Correction of enhanced endothelial permeability by cessation of cholesterol feeding (original) (raw)
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Inhibition of cholesterol-induced increases in arterial wall permeability by propranolol
Journal of Surgical Research, 1987
Increased arterial permeability to ['251]albumin is one of the earliest abnormalities found in the cholesterol-fed rabbit model for atherosclerosis and precedes morphologic changes in the arterial wall. Since propranolol is reported to retard atherogenesis in this model, the current study was undertaken to study the effect of propranolol on arterial permeability to albumin in cholesterol-fed rabbits. Carotid permeability to ['2SI]albumin was measured after 1 week of (a) a control diet containing only trace cholesterol (N = 9), (b) a 1.5% cholesterol diet (N = 1 l), or (c) a 1.5% cholesterol diet plus intraperitoneal propranolol5 mg/kg/day (N = 19). The carotid artery was cannulated proximally and distally and peristaltically perfused with oxygenated Modified Eagle's Medium to which ['251]albumin had been added. The permeability of the carotid artery to albumin was estimated by measuring '*jI activity in peripheral venous samples obtained after 0, 15, 30, 60, 120, 180, and 240 min of carotid perfusion. '251-radioactivity of the perfused carotid artery was also counted at the end of the experiment to measure '25I retained in the arterial wall. The transfer of ['2SI]albumin across the arterial wall to the venous circulation was greater in the untreated cholesterol-fed group than in controls (P < 0.05) but cholesterol-fed animals treated with propranolol did not differ significantly from controls. '251-albumin in the arterial wall after 240 min of perfusion was decreased in both untreated cholesterol-fed animals (1444 dpm/cm * 350) and in propranolol-treated animals (1629 + 309) when these were compared to controls (3909 + 693, P < .05). These data suggest that cholesterol feeding increases both the penetration of albumin into the arterial wall and its rate of clearance from the wall to the venous circulation. Furthermore, treatment with propranolol appears to prevent this increase in trans-carotid albumin flux by preventing increases in both penetration and clearance. These findings further support the hypothesis that propranolol's ability to retard atherogenesis is mediated by a direct effect on the arterial wall.
Circulation Journal, 2015
Background: Atherosclerosis is a chronic fibroproliferative disease that includes accumulation of cholesterol-rich lipids in the arterial wall. Though numerous studies have investigated atherosclerosis, not enough is known about the exact mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall. Therefore, we explored the 125 I-LDL transport into the arterial wall under constant perfusion flow and pressure as well as the influence of duration of atherogenic diet on 125 I-LDL transport and biomechanical properties of carotid artery. Methods and Results: The isolated segment of rabbit carotid artery was used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg) blood vessel distension, with the possibility to change and precisely calculate shear stress during the experiment. Obtained results indicate the influence of atherogenic diet duration and consequent variation of shear stress on 125 I-LDL transport into the blood vessel wall. 125 I-LDL transport into the blood vessel wall at low pressure-induced blood vessel distension decreases by the increase of the shear stress and in relation to the atherogenic diet duration. At high pressure-induced blood vessel distension, 125 I-LDL transport increases in relation to the atherogenic diet duration and the increase of shear stress. Conclusions: The influence of shear stress is a more dominant parameter on LDL uptake at low pressure-induced blood vessel distension; however, the atherogenic diet duration has more of a dominant influence on LDL uptake at high pressure-induced vessel distension.
Arteriosclerosis, thrombosis, and vascular biology, 2017
Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d5 and the nonabsorbable stool marker sitostanol-d4. Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickne...
Early endothelial dysfunction in cholesterol-fed rabbits: a non-invasive in vivo ultrasound study
Cardiovascular ultrasound, 2004
Endothelial function in hypercholesterolemic rabbits is usually evaluated ex vivo on isolated aortic rings. In vivo evaluation requires invasive imaging procedures that cannot be repeated serially. We evaluated a non-invasive ultrasound technique to assess early endothelial function in rabbits and compare data with ex vivo measurements. Twenty-four rabbits (fed with a cholesterol diet (0.5%) for 2 to 8 weeks) were given progressive infusions of acetylcholine (0.05-0.5 microg/kg/min) and their endothelial function was assessed in vivo by transcutaneous vascular ultrasound of the abdominal aorta. Ex vivo endothelial function was evaluated on isolated aortic rings and compared to in vivo data. Significant endothelial dysfunction was demonstrated in hypercholesterolemic animals as early as 2 weeks after beginning the cholesterol diet (aortic cross-sectional area variation: -2.9% vs. +4% for controls, p < 0.05). Unexpectedly, response to acetylcholine at 8 weeks was more variable. End...
Experimental and Toxicologic Pathology, 2013
Background and objectives: The aim of this study is to verify the evolution and involution of experimental atherosclerosis in rabbits through the study of endothelial function, lipids and tissue lipid peroxidation, macro and microscopic quantification of aortic atherosclerosis. Methods: Thirty male New Zealand white rabbits were divided into six groups (n = 5): G1 normal diet; G2: hypercholesterolemic receiving 0.5% of cholesterol diet for 4 months; G3: hypercholesterolemic diet for 4 months after normal diet for more 4 months; G4: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 1 month, G5: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 2 months, G6: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 4 months. Rosuvastatin was administered at a dosage of 5 mg dissolved in 150 ml of water daily. At the end of the experiment were measured: total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), tissue cholesterol (CAO), lipid peroxidation tissue (MDA). Endothelial function (RMAX) was studied in a segment of thoracic aorta, through curve-effect of acetylcholine and sodium nitroprusside. The amount of atherosclerosis was determined by measurement of the arterial lesion, through software, after staining with Sudan IV and histological staining. Results: In relation the water the rabbits drank 60-70 ml all day. It was seen significantly increase in all parameters at G2 both biochemical and tissue. In the group G3 it was seen significantly decrease in plasma lipids levels and tissue cholesterol. Treated groups G4, G5 and G6 all showed a decreased plasma lipid levels, only at G6 group it was noted a tissue cholesterol, tissue peroxidation and quantification of atherosclerosis, which showed a significant decrease. In relation the endothelial function only G6 improve significantly. Interpretation and conclusions: Our findings indicated that the treatment with rosuvastatin for 4 months is more efficient because improve the endothelial function significantly.
Nutrients, 2020
Hyperglycaemia has a toxic effect on blood vessels and promotes coronary artery disease. It is unclear whether the dysfunction caused by hyperglycaemia is blood vessel specific and whether the dysfunction is exacerbated following an atherogenic diet. Abdominal aorta, iliac, and mesenteric arteries were dissected from New Zealand White rabbits following either a 4-week normal or atherogenic diet (n = 6–12 per group). The arteries were incubated ex vivo in control or high glucose solution (20 mM or 40 mM) for 2 h. Isometric tension myography was used to determine endothelial-dependent vasodilation. The atherogenic diet reduced relaxation as measured by area under the curve (AUC) by 25% (p < 0.05), 17% (p = 0.06) and 40% (p = 0.07) in the aorta, iliac, and mesenteric arteries, respectively. In the aorta from the atherogenic diet fed rabbits, the 20 mM glucose altered EC50 (p < 0.05). Incubation of the iliac artery from atherogenic diet fed rabbits in 40 mM glucose altered EC50 (p...
Atherosclerosis, 2006
Endothelial dysfunction is characterized by impaired vasodilation, increase of oxidative stress and inflammation. The current study was designed to test the hypothesis that reversal of hypercholesterolemic diet alone does not normalize all the parameters of endothelial dysfunction. After 10 weeks on a high-cholesterol diet, female juvenile pigs were randomized to normal diet (n = 5, "Reversals") or continued on the same diet (n = 6, "HC") for another 6 weeks. A control group of 11 pigs received a normal diet ("C"). Coronary epicardial and arteriolar endothelial function was tested in vitro. NFB and p47phox expression was analyzed in epicardial arteries and myocardium, respectively. P47phox localization in coronary arteries was demonstrated with immunohistochemistry. Lipid levels normalized in Reversal pigs. Epicardial arteries of Reversals showed a normalized relaxation and NFB expression compared to HC (p < 0.05). Small vessel relaxation remained attenuated, and expression of p47phox in myocardial tissue was elevated in Reversals compared to C (p < 0.05). Dietary lowering of serum cholesterol and LDL improves vascular function of epicardial arteries but neither of small vessels nor vascular oxidative stress within this time frame. Hence, dietary normalization of serum lipid levels alone may not be synonymous to normalization of the components of endothelial dysfunction.
Cholesterol vehicle in experimental atherosclerosis
Atherosclerosis, 1977
Randomized lard and butter oil were compared with native lard and butter oil for their effects on cholesterol-induced atherosclerosis in rabbits. In each experiment there was also a group fed corn oil. The diets contained 2% cholesterol and 6% fat and were fed for eight weeks. Randomization of either butter or lard had virtually no effect as regards their atherogenic potential when fed as part of a diet containing 2% cholesterol. The corn oil-containing diet was less atherogenic than any of the other fats.