Anita Ćosić - Academia.edu (original) (raw)

Papers by Anita Ćosić

Research paper thumbnail of The Effects of AT1 Receptor Blockade on Skin Microcirculatory Blood Flow and Thromboxane A2 (TXA2) Production in Young Healthy Women

The FASEB Journal

AT1 receptor activation has an important role in maintaining the vascular release of prostaglandi... more AT1 receptor activation has an important role in maintaining the vascular release of prostaglandins responsible for mediating hypoxic dilation in skeletal muscle microvessels in normotensive rats. High salt diet leads to impairment of vasodilator responses that could be restored by infusion of subpressor dose of ANG II via its interaction with AT1 receptors. In addition to AT1 receptors blockade, losartan blocks thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor. The aim of this study was to determine the effect of one week AT1 receptor blockade by losartan in 10 healthy normotensive women (20±2 years old) on law salt diet (LSD) on post occlusive hyperemic blood flow response in skin microcirculation by Laser Doppler Flowmetry (LDF) and to determine the plasma renin activity (PRA) and plasma thromboxane A2 (TXA2) concentration. Participants maintained LSD (<40 mmol of Na/day) and took 50 mg of losartan/day for 7 days. After one week of losartan administration the post occlusive hyperemic tissue blood flow was unchanged. However, plasma PRA and TXA2 levels were significantly increased compared to pre-losartan values. Our results indicate that although one week of AT1 receptor blockade increases the plasma TXA2 concentration and PRA, the skin microcirculatory blood flow remained unchanged, possibly due to losartan blockade of TXA2 receptors and ANG II interaction with AT2 receptors.

Research paper thumbnail of Changes in serum levels of inflammatory biomarkers in patients with acute and chronic coronary syndrome consuming n-3 PUFA enriched hen eggs- a randomized study

Annual meeting of the Croatian Immunological Society 2021, 2021

Research paper thumbnail of The effect of n-3 PUFA dietary supplementation on hemorheology, endothelium-dependent microvascular function and on physical performance

Research paper thumbnail of The influence of habitual salt intake on bone remodelling in young healthy people

Slovenian Medical Journal, 2021

Introduction: Sodium alters calcium metabolism by increasing calcium excretion, thus possibly inf... more Introduction: Sodium alters calcium metabolism by increasing calcium excretion, thus possibly influencing bone metabolism. The hypothesis of the present study is that amount of dietary sodium intake affects the bone remodelling. This study aimed to assess whether a habitual intake of sodium has an effect on peak bone mass and biochemical indicators of bone metabolism. Subjects and Methods: In a cross-sectional study that involved 41 young men and women, six biochemical markers were assessed from blood samples using ELISA: osteocalcin, C-terminal procollagen type I peptide, receptor activator kappa B ligand, pyridinoline, parathyroid hormone, and osteoprotegerin, while bone mineral density (BMD) and bone mineral content (BMC) were measured by dual x-ray absorptiometry. Subjects were divided into two groups according to habitual sodium intake (low-Na and high-Na group) assessed by questionnaire. Results: No difference was found between groups of low and high Na intake in BMD and BMC, ...

Research paper thumbnail of Functional food in cardiovascular protection- effects of n-3 polyunsaturated fatt acids

Research paper thumbnail of Anti-Inflammatory Potential of n-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption in Improving Microvascular Endothelial Function of Healthy Individuals—Clinical Trial

International Journal of Molecular Sciences, 2020

The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on en... more The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on endothelium-dependent and endothelium-independent vasodilation in microcirculation, and on endothelial activation and inflammation were determined in young healthy individuals. Control group (N = 21) ate three regular hen eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N = 19) ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Skin microvascular blood flow in response to iontophoresis of acetylcholine (AChID; endothelium-dependent) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, and inflammatory and endothelial activation markers were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs concentration significantly increased, AChID significantly improved, and SNPID remained uncha...

Research paper thumbnail of Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3−/−/C57BL/6N Knockout and WT (C57BL/6N) Control Mice

International Journal of Molecular Sciences, 2019

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to vario... more High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3−/− gene knockout mice (Tff3−/−/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3−/− and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3−/−-HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3−/− mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency...

Research paper thumbnail of The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats

International Journal of Endocrinology, 2019

Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular... more Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results. AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was signifi...

Research paper thumbnail of Omega-3 polyunsaturated fatty acids-enriched hen eggs consumption enhances microvascular reactivity in young healthy individuals

Applied Physiology, Nutrition, and Metabolism, 2018

The beneficial effect of omega-3 polyunsaturated fatty acids (PUFA) supplementation on the cardio... more The beneficial effect of omega-3 polyunsaturated fatty acids (PUFA) supplementation on the cardiovascular (CV) system is well supported in CV patients; however, the effect of the consumption of omega-3 PUFA-enriched functional food in healthy individuals is still not fully elucidated. This study aimed to determine the effect of the consumption of omega-3 PUFA-enriched hen eggs on the microvascular reactivity (primary outcome), blood pressure (BP), and serum lipid profile in young healthy individuals. The control group (N = 16) ate 3 ordinary hen eggs (277 mg of omega-3 PUFAs/day), and the OMEGA-3 group (N = 20) ate 3 omega-3 PUFA-enriched eggs containing 259 mg of omega-3 PUFAs/egg daily (α-linolenic acid (ALA), 167 mg/egg; eicosapentaenoic acid (EPA), 7 mg/egg; docosahexaenoic acid (DHA), 84 mg/egg) for 3 weeks (777 mg of omega-3 PUFA/day). Postocclusive reactive hyperemia (PORH) in skin microcirculation assessed by laser Doppler flowmetry, serum lipid profile, fasting blood glucos...

Research paper thumbnail of The Role of Oxidative Stress in Development of Impaired Vascular Response Under the Influence of High Sodium Chloride Intake in Sprague-Dawley Rats

Cilj: Utvrditi bazični odgovor i razjasniti mehanizme protokom posredovane dilatacije (FID) te iz... more Cilj: Utvrditi bazični odgovor i razjasniti mehanizme protokom posredovane dilatacije (FID) te izražaj antioksidativnih gena, gena uključenih u dilatacijske putove središnje moždane arterije (MCA), razinu leukocitne aktivacije i ulogu oksidativnog stresa u MCA kod Spraque-Dawley (SD) štakora na visokoslanoj (VS) dijeti. Metode: Zdravi muški SD štakori starosti 11 tjedana hranjeni su standardnom hranom (0,4% NaCl, NS grupa) ili hranom s 4% NaCl (VS grupa) tjedan dana, s ili bez dodatka TEMPOLA in vivo. Reaktivnost MCA u odgovoru na stupnjevito povećanje protoka izmjerena je u odsutnosti ili prisutnosti inhibitora sintaze dušičnog oksida (L-NAME), ciklooksigenaze 1 i 2 (COX-1,2) indometacina (INDO), selektivnog inhibitora CYP450 epoksidaze (MS-PPOH) i „hvatača“ superoksidnih radikala TEMPOLA. mRNA izražaj antioksidativnih enzima (SOD izoformi, glutation peroksidaze 1 i 4 (GPx 1 i GPx4), katalaze (CAT)) i gena uključenih u dilatacijske putove ((COX-1, 2, hipoksijom inducirani faktor 1 ...

![Research paper thumbnail of Influence of high salt diet on the interrelation of HIF-1` and antioxidative genes in microcirculation of Sprague-Dawley rats](https://a.academia-assets.com/images/blank-paper.jpg)

Physiology, 2016

Our recent data showed that mRNA expression of hypoxia inducible factor 1 alpha (HIF-1α) in brain... more Our recent data showed that mRNA expression of hypoxia inducible factor 1 alpha (HIF-1α) in brain blood vessels (BBV) depends on the level of superoxide and suggested that COX-2 can be interrelated with HIF-1α (1). This study aimed to assess the effects of HS and a superoxide scavenger TEMPOL (T) on expression of antioxidative genes (Cu/ZnSOD, MnSOD, EC-SOD, catalase (CAT) and glutathione-peroxidase 1 and 4 (GPx1 and GPx4)) in regard to HIF-1α expression and their interrelation to each others in microcirculation. Four groups of 11- weeks old healthy male Sprague- Dawley rats were included in the study: low salt group (LS ; standard rat chow (0.4% NaCl) and HS group (4% NaCl in chow) for 1 week with or without TEMPOL in vivo (drinking water, 1nM/L) (LS+T and HS+T). Following diet protocol, rats were anesthetized with ketamine (75 mg/kg) and midazolam (2.5 mg/kg) decapitated and their BBV were harvested. mRNA levels were determined by real-time qPCR. Data were analyzed by Oneway ANOVA (SigmaPlot 11.0) and MANOVA test (IBM SPSS Statistics 20). p<0.05 was considered significant. All experimental procedures conformed to the European Guidelines (Directive 86/609) and were approved by the local Ethical Committee (Class:602- 04/14-08/06, #2158-61-07- 14-04). Expression of MnSOD and CAT was significantly increased in LS+T group compared to other groups (p<0.05). Cu/Zn SOD, EC-SOD and GPx4 expression was decreased in HS and LS groups compared to LS+T group and Cu/Zn SOD, EC-SOD, GPx4 expression were decreased in HS group compared to HS+T and to LS+T (<0.001). EC-SOD expression was decreased in LS group compared to HS+T group (p<0.05). GPx1 expression increased in LS and HS compared to HS+T (p<0.001, p=0.002 respectively). Expression of HIF-1α was significantly increased in both T groups compared to both, LS and HS group (LS vs. LS+T p=0.005 ; LS vs. HS+T p=0.042 ; HS vs. LS+T p<0.001 ; HS vs. HS+T p=0.003). Correlations of HIF-1α with antioxidative genes were found only in HS and HS-T groups. In HS group, HIF-1α positively correlated with MnSOD (r=0.935, p=0.002) and GPx1 (r=0.834, p=0.02) and in HS+T group with CAT (r=0.925, p=0.024). Positive correlation of HIF-1α gene expression with the antioxidative enzymes in HS groups suggests that a longer period of NaCl intake could significantly modify its expression. The expression of HIF-1α gene depends largely on expression of MnSOD (2). Since the expression of MnSOD did not significantly change compared in HS diet to LS diet, it is possible that this is additional reason for unchanged HIF-1α expression. Increased expression of HIF-1α in TEMPOL, together with increased MnSOD expression suggest that HIF-1α expression depends on other antioxidant genes’ expression and the level of oxidative stress. A. Cosic, S. Novak, A. Cavka, Z. Mihaljevic, I. Jukic (ex Grizelj), M. Mihalj, I. Drenjancevic. ROLE OF TEMPOL ON THE LEVEL OF OXIDATIVE STRESS AND GENE EXPRESSION IN HIGH SALT DIET FED SPRAGUE-DAWLEY RATS, ESH2015, Milano Kaewpila S, Venkataraman S, Buettner GR, Oberley LW. Manganese Superoxide Dismutase Modulates Hypoxia- Inducible Factor- 1α Induction via Superoxide. Cancer Res. 2008 ; 68(8): 2781–2788. Funding in part by Croatian Science Foundation grant #IP-2014-09-6380. Where applicable, the authors confirm that the experiments described here conform with the Physiological Society ethical requirements.

Research paper thumbnail of Does the endothelium of competitive athletes benefit from the consumption of n-3 polyunsaturated fatty acids-enriched hen eggs? – Paper presentation

Science 4 Health Book of Abstracts, 2021

Research paper thumbnail of The Markers of Endothelial Activation

Endothelial Dysfunction - Old Concepts and New Challenges, 2018

Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the disea... more Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the diseases, and can, but do not have to be causal to diseases. One very important question is how specific and sensitive the marker is, since one molecule can appear in many conditions. Biomarkers of endothelial cell activation can be very diverse, from biochemical/ metabolic to functional biomarkers. Activation of endothelial cells is part of physiological as well as pathophysiological response of cardiovascular system in conditions as physical activity, growth, pregnancy and in all cardiometabolic diseases (e.g., hypertension, diabetes mellitus, autoimmune inflammatory diseases, coronary artery disease, atherosclerosis, ischemia and reperfusion, etc.). During activation, there is a change in endothelial cell morphology and function, which could be a defensive response of endothelium to provoking factor or could lead to increased risk for the injury and end organ damage. This chapter aims to overview current knowledge on established biomarkers of normal and disease-related endothelial activation and to provide information on novel, potential biomarkers in common cardiometabolic diseases.

Research paper thumbnail of Effect of n-3 polyunsaturated fatty acid-enriched chicken eggs consumption in patients with known atherosclerotic coronary artery disease on pro-inflammatory cytokines

Research paper thumbnail of Angiotensin II effect on dynamics of leukocyte's subpopulations in rats on short-term high salt diet

Research paper thumbnail of Temeljni mehanizmi i manifestacije endotelne disfunkcije u autoimunim bolestima

Research paper thumbnail of Acute salt loading affects post-occlusive reactive hyperemia in skin microcirculation independently of blood pressure changes in young healthy men

Journal of Vascular Research, 2017

Research paper thumbnail of The role of angiotensin -1 receptors in vasodilator responses of middle cerebral arteries in Sprague- Dawley rats

Research paper thumbnail of Acute exposure to hyperbaric oxygenation impaires endothelial nitric oxide production in Sprague-Dawley healthy male rats

Research paper thumbnail of Pozitivan utjecaj konzumacije omega-3 obogaćenih jaja na smanjenje razina oksidativnog stresa kod mladih zdravih ženskih ispitanica

Research paper thumbnail of The Effects of AT1 Receptor Blockade on Skin Microcirculatory Blood Flow and Thromboxane A2 (TXA2) Production in Young Healthy Women

The FASEB Journal

AT1 receptor activation has an important role in maintaining the vascular release of prostaglandi... more AT1 receptor activation has an important role in maintaining the vascular release of prostaglandins responsible for mediating hypoxic dilation in skeletal muscle microvessels in normotensive rats. High salt diet leads to impairment of vasodilator responses that could be restored by infusion of subpressor dose of ANG II via its interaction with AT1 receptors. In addition to AT1 receptors blockade, losartan blocks thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor. The aim of this study was to determine the effect of one week AT1 receptor blockade by losartan in 10 healthy normotensive women (20±2 years old) on law salt diet (LSD) on post occlusive hyperemic blood flow response in skin microcirculation by Laser Doppler Flowmetry (LDF) and to determine the plasma renin activity (PRA) and plasma thromboxane A2 (TXA2) concentration. Participants maintained LSD (<40 mmol of Na/day) and took 50 mg of losartan/day for 7 days. After one week of losartan administration the post occlusive hyperemic tissue blood flow was unchanged. However, plasma PRA and TXA2 levels were significantly increased compared to pre-losartan values. Our results indicate that although one week of AT1 receptor blockade increases the plasma TXA2 concentration and PRA, the skin microcirculatory blood flow remained unchanged, possibly due to losartan blockade of TXA2 receptors and ANG II interaction with AT2 receptors.

Research paper thumbnail of Changes in serum levels of inflammatory biomarkers in patients with acute and chronic coronary syndrome consuming n-3 PUFA enriched hen eggs- a randomized study

Annual meeting of the Croatian Immunological Society 2021, 2021

Research paper thumbnail of The effect of n-3 PUFA dietary supplementation on hemorheology, endothelium-dependent microvascular function and on physical performance

Research paper thumbnail of The influence of habitual salt intake on bone remodelling in young healthy people

Slovenian Medical Journal, 2021

Introduction: Sodium alters calcium metabolism by increasing calcium excretion, thus possibly inf... more Introduction: Sodium alters calcium metabolism by increasing calcium excretion, thus possibly influencing bone metabolism. The hypothesis of the present study is that amount of dietary sodium intake affects the bone remodelling. This study aimed to assess whether a habitual intake of sodium has an effect on peak bone mass and biochemical indicators of bone metabolism. Subjects and Methods: In a cross-sectional study that involved 41 young men and women, six biochemical markers were assessed from blood samples using ELISA: osteocalcin, C-terminal procollagen type I peptide, receptor activator kappa B ligand, pyridinoline, parathyroid hormone, and osteoprotegerin, while bone mineral density (BMD) and bone mineral content (BMC) were measured by dual x-ray absorptiometry. Subjects were divided into two groups according to habitual sodium intake (low-Na and high-Na group) assessed by questionnaire. Results: No difference was found between groups of low and high Na intake in BMD and BMC, ...

Research paper thumbnail of Functional food in cardiovascular protection- effects of n-3 polyunsaturated fatt acids

Research paper thumbnail of Anti-Inflammatory Potential of n-3 Polyunsaturated Fatty Acids Enriched Hen Eggs Consumption in Improving Microvascular Endothelial Function of Healthy Individuals—Clinical Trial

International Journal of Molecular Sciences, 2020

The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on en... more The effects of consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) enriched hen eggs on endothelium-dependent and endothelium-independent vasodilation in microcirculation, and on endothelial activation and inflammation were determined in young healthy individuals. Control group (N = 21) ate three regular hen eggs/daily (249 mg n-3 PUFAs/day), and n-3 PUFAs group (N = 19) ate three n-3 PUFAs enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Skin microvascular blood flow in response to iontophoresis of acetylcholine (AChID; endothelium-dependent) and sodium nitroprusside (SNPID; endothelium-independent) was assessed by laser Doppler flowmetry. Blood pressure (BP), body composition, body fluid status, serum lipid and free fatty acids profile, and inflammatory and endothelial activation markers were measured before and after respective dietary protocol. Results: Serum n-3 PUFAs concentration significantly increased, AChID significantly improved, and SNPID remained uncha...

Research paper thumbnail of Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3−/−/C57BL/6N Knockout and WT (C57BL/6N) Control Mice

International Journal of Molecular Sciences, 2019

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to vario... more High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3−/− gene knockout mice (Tff3−/−/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3−/− and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3−/−-HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3−/− mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency...

Research paper thumbnail of The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats

International Journal of Endocrinology, 2019

Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular... more Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results. AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was signifi...

Research paper thumbnail of Omega-3 polyunsaturated fatty acids-enriched hen eggs consumption enhances microvascular reactivity in young healthy individuals

Applied Physiology, Nutrition, and Metabolism, 2018

The beneficial effect of omega-3 polyunsaturated fatty acids (PUFA) supplementation on the cardio... more The beneficial effect of omega-3 polyunsaturated fatty acids (PUFA) supplementation on the cardiovascular (CV) system is well supported in CV patients; however, the effect of the consumption of omega-3 PUFA-enriched functional food in healthy individuals is still not fully elucidated. This study aimed to determine the effect of the consumption of omega-3 PUFA-enriched hen eggs on the microvascular reactivity (primary outcome), blood pressure (BP), and serum lipid profile in young healthy individuals. The control group (N = 16) ate 3 ordinary hen eggs (277 mg of omega-3 PUFAs/day), and the OMEGA-3 group (N = 20) ate 3 omega-3 PUFA-enriched eggs containing 259 mg of omega-3 PUFAs/egg daily (α-linolenic acid (ALA), 167 mg/egg; eicosapentaenoic acid (EPA), 7 mg/egg; docosahexaenoic acid (DHA), 84 mg/egg) for 3 weeks (777 mg of omega-3 PUFA/day). Postocclusive reactive hyperemia (PORH) in skin microcirculation assessed by laser Doppler flowmetry, serum lipid profile, fasting blood glucos...

Research paper thumbnail of The Role of Oxidative Stress in Development of Impaired Vascular Response Under the Influence of High Sodium Chloride Intake in Sprague-Dawley Rats

Cilj: Utvrditi bazični odgovor i razjasniti mehanizme protokom posredovane dilatacije (FID) te iz... more Cilj: Utvrditi bazični odgovor i razjasniti mehanizme protokom posredovane dilatacije (FID) te izražaj antioksidativnih gena, gena uključenih u dilatacijske putove središnje moždane arterije (MCA), razinu leukocitne aktivacije i ulogu oksidativnog stresa u MCA kod Spraque-Dawley (SD) štakora na visokoslanoj (VS) dijeti. Metode: Zdravi muški SD štakori starosti 11 tjedana hranjeni su standardnom hranom (0,4% NaCl, NS grupa) ili hranom s 4% NaCl (VS grupa) tjedan dana, s ili bez dodatka TEMPOLA in vivo. Reaktivnost MCA u odgovoru na stupnjevito povećanje protoka izmjerena je u odsutnosti ili prisutnosti inhibitora sintaze dušičnog oksida (L-NAME), ciklooksigenaze 1 i 2 (COX-1,2) indometacina (INDO), selektivnog inhibitora CYP450 epoksidaze (MS-PPOH) i „hvatača“ superoksidnih radikala TEMPOLA. mRNA izražaj antioksidativnih enzima (SOD izoformi, glutation peroksidaze 1 i 4 (GPx 1 i GPx4), katalaze (CAT)) i gena uključenih u dilatacijske putove ((COX-1, 2, hipoksijom inducirani faktor 1 ...

![Research paper thumbnail of Influence of high salt diet on the interrelation of HIF-1` and antioxidative genes in microcirculation of Sprague-Dawley rats](https://a.academia-assets.com/images/blank-paper.jpg)

Physiology, 2016

Our recent data showed that mRNA expression of hypoxia inducible factor 1 alpha (HIF-1α) in brain... more Our recent data showed that mRNA expression of hypoxia inducible factor 1 alpha (HIF-1α) in brain blood vessels (BBV) depends on the level of superoxide and suggested that COX-2 can be interrelated with HIF-1α (1). This study aimed to assess the effects of HS and a superoxide scavenger TEMPOL (T) on expression of antioxidative genes (Cu/ZnSOD, MnSOD, EC-SOD, catalase (CAT) and glutathione-peroxidase 1 and 4 (GPx1 and GPx4)) in regard to HIF-1α expression and their interrelation to each others in microcirculation. Four groups of 11- weeks old healthy male Sprague- Dawley rats were included in the study: low salt group (LS ; standard rat chow (0.4% NaCl) and HS group (4% NaCl in chow) for 1 week with or without TEMPOL in vivo (drinking water, 1nM/L) (LS+T and HS+T). Following diet protocol, rats were anesthetized with ketamine (75 mg/kg) and midazolam (2.5 mg/kg) decapitated and their BBV were harvested. mRNA levels were determined by real-time qPCR. Data were analyzed by Oneway ANOVA (SigmaPlot 11.0) and MANOVA test (IBM SPSS Statistics 20). p<0.05 was considered significant. All experimental procedures conformed to the European Guidelines (Directive 86/609) and were approved by the local Ethical Committee (Class:602- 04/14-08/06, #2158-61-07- 14-04). Expression of MnSOD and CAT was significantly increased in LS+T group compared to other groups (p<0.05). Cu/Zn SOD, EC-SOD and GPx4 expression was decreased in HS and LS groups compared to LS+T group and Cu/Zn SOD, EC-SOD, GPx4 expression were decreased in HS group compared to HS+T and to LS+T (<0.001). EC-SOD expression was decreased in LS group compared to HS+T group (p<0.05). GPx1 expression increased in LS and HS compared to HS+T (p<0.001, p=0.002 respectively). Expression of HIF-1α was significantly increased in both T groups compared to both, LS and HS group (LS vs. LS+T p=0.005 ; LS vs. HS+T p=0.042 ; HS vs. LS+T p<0.001 ; HS vs. HS+T p=0.003). Correlations of HIF-1α with antioxidative genes were found only in HS and HS-T groups. In HS group, HIF-1α positively correlated with MnSOD (r=0.935, p=0.002) and GPx1 (r=0.834, p=0.02) and in HS+T group with CAT (r=0.925, p=0.024). Positive correlation of HIF-1α gene expression with the antioxidative enzymes in HS groups suggests that a longer period of NaCl intake could significantly modify its expression. The expression of HIF-1α gene depends largely on expression of MnSOD (2). Since the expression of MnSOD did not significantly change compared in HS diet to LS diet, it is possible that this is additional reason for unchanged HIF-1α expression. Increased expression of HIF-1α in TEMPOL, together with increased MnSOD expression suggest that HIF-1α expression depends on other antioxidant genes’ expression and the level of oxidative stress. A. Cosic, S. Novak, A. Cavka, Z. Mihaljevic, I. Jukic (ex Grizelj), M. Mihalj, I. Drenjancevic. ROLE OF TEMPOL ON THE LEVEL OF OXIDATIVE STRESS AND GENE EXPRESSION IN HIGH SALT DIET FED SPRAGUE-DAWLEY RATS, ESH2015, Milano Kaewpila S, Venkataraman S, Buettner GR, Oberley LW. Manganese Superoxide Dismutase Modulates Hypoxia- Inducible Factor- 1α Induction via Superoxide. Cancer Res. 2008 ; 68(8): 2781–2788. Funding in part by Croatian Science Foundation grant #IP-2014-09-6380. Where applicable, the authors confirm that the experiments described here conform with the Physiological Society ethical requirements.

Research paper thumbnail of Does the endothelium of competitive athletes benefit from the consumption of n-3 polyunsaturated fatty acids-enriched hen eggs? – Paper presentation

Science 4 Health Book of Abstracts, 2021

Research paper thumbnail of The Markers of Endothelial Activation

Endothelial Dysfunction - Old Concepts and New Challenges, 2018

Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the disea... more Biomarkers are biological indicators of processes that are part of ethiopathogenesis of the diseases, and can, but do not have to be causal to diseases. One very important question is how specific and sensitive the marker is, since one molecule can appear in many conditions. Biomarkers of endothelial cell activation can be very diverse, from biochemical/ metabolic to functional biomarkers. Activation of endothelial cells is part of physiological as well as pathophysiological response of cardiovascular system in conditions as physical activity, growth, pregnancy and in all cardiometabolic diseases (e.g., hypertension, diabetes mellitus, autoimmune inflammatory diseases, coronary artery disease, atherosclerosis, ischemia and reperfusion, etc.). During activation, there is a change in endothelial cell morphology and function, which could be a defensive response of endothelium to provoking factor or could lead to increased risk for the injury and end organ damage. This chapter aims to overview current knowledge on established biomarkers of normal and disease-related endothelial activation and to provide information on novel, potential biomarkers in common cardiometabolic diseases.

Research paper thumbnail of Effect of n-3 polyunsaturated fatty acid-enriched chicken eggs consumption in patients with known atherosclerotic coronary artery disease on pro-inflammatory cytokines

Research paper thumbnail of Angiotensin II effect on dynamics of leukocyte's subpopulations in rats on short-term high salt diet

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Journal of Vascular Research, 2017

Research paper thumbnail of The role of angiotensin -1 receptors in vasodilator responses of middle cerebral arteries in Sprague- Dawley rats

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