Gopi Krishna Kolluru - Academia.edu (original) (raw)
Papers by Gopi Krishna Kolluru
Redox biology, May 1, 2018
Hydrogen sulfide (HS) has emerged as an important physiological and pathophysiological signaling ... more Hydrogen sulfide (HS) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of HS in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of HS in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of HS. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfu...
Journal of pregnancy, 2017
MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttran... more MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are "fine-tuners" rather than "switches" in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-...
Journal of proteome research, Oct 20, 2016
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hyp... more Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and ...
Circulation, Nov 26, 2013
Circulation, Nov 22, 2011
Circulation, Nov 25, 2014
Introduction: Aging is a major risk factor for cardiovascular diseases (CVD) and is associated wi... more Introduction: Aging is a major risk factor for cardiovascular diseases (CVD) and is associated with complications including oxidative stress and inflammation. Hydrogen sulfide (H2S) and Nitric Oxide (NO) are gaseous signaling molecules implicated in numerous pathophysiological functions of the vasculature. CSE genetic deficiency and subsequent reduction in H2S levels attenuates ischemic vascular remodeling. Additionally, sirtuin1 (Sirt1) critically regulates mechanisms of angiogenesis, inflammation and cardioprotection. However, the importance of CSE/H2S in relation to age-dependent dysfunctions has not been investigated. Objective: To investigate the age-dependent regulation of H2S and NO metabolites in aged mice and the rescue mechanisms mediated upon H2S therapy in aged mice ischemic hind limb model. Methods: Unilateral femoral artery ligation was performed on 52-week-old CSE-/- mice, which were treated with PBS or H2S donor DATS (200μg/kg) administered retro-orbitally twice daily until Day 7. Hind lim...
The Faseb Journal, Apr 1, 2011
Journal of Applied Physiology, 2015
Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 lev... more Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 levels leads to changes in molecular signaling and ultimately affects the physiological functions of many organisms. Nitric oxide (NO) and hydrogen sulfide (H2S) are two gaseous cellular signaling molecules that play key roles in several physiological functions involved in maintaining vascular homeostasis including vasodilation, anti-inflammation, and vascular growth. Apart from the aforementioned functions, NO and H2S are believed to mediate hypoxic responses and serve as O2 chemosensors in biological systems. In this literature review, we briefly discuss NO and H2S and their roles during hypoxia.
Cardiovascular research, Jan 20, 2015
Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vascu... more Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischemic vascular remodeling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischemic vascular remodeling involving H2S dependent mononuclear cell regulation of arteriogenesis. Arteriogenesis including mature vessel density, collateral formation; blood flow and SPY angiographic blush rate were determined in WT and CSE knockout mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischemic tissues, were determined along with EPC (CD34/Flk1) formation and function. FAL of wild type mice significantly increased CSE activity, expression and endogenous H2S generation in isch...
Journal of the American Heart Association, 2012
Hydrogen sulfide (H(2)S) therapy is recognized as a modulator of vascular function during tissue ... more Hydrogen sulfide (H(2)S) therapy is recognized as a modulator of vascular function during tissue ischemia with the notion of potential interactions of nitric oxide (NO) metabolism. However, little is known about specific biochemical mechanisms or the importance of H(2)S activation of NO metabolism during ischemic tissue vascular remodeling. The goal of this study was to determine the effect of H(2)S on NO metabolism during chronic tissue ischemia and subsequent effects on ischemic vascular remodeling responses. The unilateral, permanent femoral artery ligation model of hind-limb ischemia was performed in C57BL/6J wild-type and endothelial NO synthase-knockout mice to evaluate exogenous H(2)S effects on NO bioavailability and ischemic revascularization. We found that H(2)S selectively restored chronic ischemic tissue function and viability by enhancing NO production involving both endothelial NO synthase and nitrite reduction mechanisms. Importantly, H(2)S increased ischemic tissue x...
International Journal of Vascular Medicine, 2012
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycem... more Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of di...
BMC cell biology, Jan 4, 2006
Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angio... more Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angiogenic activity of thalidomide is not fully understood. As nitric oxide is involved in angiogenesis, we speculate a cross-talk between thalidomide and nitric oxide signaling pathway to define angiogenesis. The aim of present study is to understand the mechanistic aspects of thalidomide-mediated attenuation of angiogenesis induced by nitric oxide at the cellular level. To study the cellular mechanism of thalidomide-mediated blocking of angiogenesis triggered by nitric oxide, we used two endothelial cell based models: 1) wound healing and 2) tube formation using ECV 304, an endothelial cell line. These cell-based models reflect pro-angiogenic events in vivo. We also studied the effects of thalidomide on nitric oxide mediated egg yolk angiogenesis. Thalidomide could block the formation of blood vessels both in absence and presence of nitric oxide. Thalidomide effects on migration of, and act...
Vascular and Endovascular Surgery, 2013
Purpose: To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney... more Purpose: To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney 2 (HK-2). Methods: The HK-2 cells were treated with Iodixanol. A Terminal deoxynucleotidyl transferase dUTP nick-end labeling ( TUNEL) assay was used to evaluate apoptosis. Cell viability was measured by proliferation assay kit. Cell permeability changes were assessed by transwell assay and intercellular gaps measurement. Expression of claudin-2 was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Results: Iodixanol reduced tubule cell viability ( P < .01) but did not cause apoptosis. The intercellular gap formation ( P < .01) and transwell ( P < .05) assays revealed that cell permeability significantly increased after Iodixanol treatment of monolayer cells. Western blot and qRT-PCR showed significant upregulation of claudin-2 protein ( P < .05) and messenger RNA expression ( P < .01). Conclusions: Our in vitro data do n...
Redox biology, May 1, 2018
Hydrogen sulfide (HS) has emerged as an important physiological and pathophysiological signaling ... more Hydrogen sulfide (HS) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of HS in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of HS in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of HS. Single nucleotide polymorphisms (SNPs) were also identified using DNA Pyrosequencing. We found that plasma acid labile sulfide levels were significantly reduced in Caucasian females with CVD compared with those without the disease. Conversely, plasma bound sulfane sulfu...
Journal of pregnancy, 2017
MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttran... more MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are "fine-tuners" rather than "switches" in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-...
Journal of proteome research, Oct 20, 2016
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hyp... more Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and ...
Circulation, Nov 26, 2013
Circulation, Nov 22, 2011
Circulation, Nov 25, 2014
Introduction: Aging is a major risk factor for cardiovascular diseases (CVD) and is associated wi... more Introduction: Aging is a major risk factor for cardiovascular diseases (CVD) and is associated with complications including oxidative stress and inflammation. Hydrogen sulfide (H2S) and Nitric Oxide (NO) are gaseous signaling molecules implicated in numerous pathophysiological functions of the vasculature. CSE genetic deficiency and subsequent reduction in H2S levels attenuates ischemic vascular remodeling. Additionally, sirtuin1 (Sirt1) critically regulates mechanisms of angiogenesis, inflammation and cardioprotection. However, the importance of CSE/H2S in relation to age-dependent dysfunctions has not been investigated. Objective: To investigate the age-dependent regulation of H2S and NO metabolites in aged mice and the rescue mechanisms mediated upon H2S therapy in aged mice ischemic hind limb model. Methods: Unilateral femoral artery ligation was performed on 52-week-old CSE-/- mice, which were treated with PBS or H2S donor DATS (200μg/kg) administered retro-orbitally twice daily until Day 7. Hind lim...
The Faseb Journal, Apr 1, 2011
Journal of Applied Physiology, 2015
Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 lev... more Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 levels leads to changes in molecular signaling and ultimately affects the physiological functions of many organisms. Nitric oxide (NO) and hydrogen sulfide (H2S) are two gaseous cellular signaling molecules that play key roles in several physiological functions involved in maintaining vascular homeostasis including vasodilation, anti-inflammation, and vascular growth. Apart from the aforementioned functions, NO and H2S are believed to mediate hypoxic responses and serve as O2 chemosensors in biological systems. In this literature review, we briefly discuss NO and H2S and their roles during hypoxia.
Cardiovascular research, Jan 20, 2015
Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vascu... more Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously produced in the vasculature by the enzyme cystathionine γ-lyase (CSE). However, the importance of CSE activity and local H2S generation for ischemic vascular remodeling remains completely unknown. In this study, we examine the hypothesis that CSE critically regulates ischemic vascular remodeling involving H2S dependent mononuclear cell regulation of arteriogenesis. Arteriogenesis including mature vessel density, collateral formation; blood flow and SPY angiographic blush rate were determined in WT and CSE knockout mice at different time points following femoral artery ligation (FAL). The role of endogenous H2S in regulation of IL-16 expression and subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischemic tissues, were determined along with EPC (CD34/Flk1) formation and function. FAL of wild type mice significantly increased CSE activity, expression and endogenous H2S generation in isch...
Journal of the American Heart Association, 2012
Hydrogen sulfide (H(2)S) therapy is recognized as a modulator of vascular function during tissue ... more Hydrogen sulfide (H(2)S) therapy is recognized as a modulator of vascular function during tissue ischemia with the notion of potential interactions of nitric oxide (NO) metabolism. However, little is known about specific biochemical mechanisms or the importance of H(2)S activation of NO metabolism during ischemic tissue vascular remodeling. The goal of this study was to determine the effect of H(2)S on NO metabolism during chronic tissue ischemia and subsequent effects on ischemic vascular remodeling responses. The unilateral, permanent femoral artery ligation model of hind-limb ischemia was performed in C57BL/6J wild-type and endothelial NO synthase-knockout mice to evaluate exogenous H(2)S effects on NO bioavailability and ischemic revascularization. We found that H(2)S selectively restored chronic ischemic tissue function and viability by enhancing NO production involving both endothelial NO synthase and nitrite reduction mechanisms. Importantly, H(2)S increased ischemic tissue x...
International Journal of Vascular Medicine, 2012
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycem... more Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of di...
BMC cell biology, Jan 4, 2006
Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angio... more Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angiogenic activity of thalidomide is not fully understood. As nitric oxide is involved in angiogenesis, we speculate a cross-talk between thalidomide and nitric oxide signaling pathway to define angiogenesis. The aim of present study is to understand the mechanistic aspects of thalidomide-mediated attenuation of angiogenesis induced by nitric oxide at the cellular level. To study the cellular mechanism of thalidomide-mediated blocking of angiogenesis triggered by nitric oxide, we used two endothelial cell based models: 1) wound healing and 2) tube formation using ECV 304, an endothelial cell line. These cell-based models reflect pro-angiogenic events in vivo. We also studied the effects of thalidomide on nitric oxide mediated egg yolk angiogenesis. Thalidomide could block the formation of blood vessels both in absence and presence of nitric oxide. Thalidomide effects on migration of, and act...
Vascular and Endovascular Surgery, 2013
Purpose: To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney... more Purpose: To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney 2 (HK-2). Methods: The HK-2 cells were treated with Iodixanol. A Terminal deoxynucleotidyl transferase dUTP nick-end labeling ( TUNEL) assay was used to evaluate apoptosis. Cell viability was measured by proliferation assay kit. Cell permeability changes were assessed by transwell assay and intercellular gaps measurement. Expression of claudin-2 was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Results: Iodixanol reduced tubule cell viability ( P < .01) but did not cause apoptosis. The intercellular gap formation ( P < .01) and transwell ( P < .05) assays revealed that cell permeability significantly increased after Iodixanol treatment of monolayer cells. Western blot and qRT-PCR showed significant upregulation of claudin-2 protein ( P < .05) and messenger RNA expression ( P < .01). Conclusions: Our in vitro data do n...