scholarly journals INTRACORONARY AUTOLOGOUS CD34+ CELL THERAPY FOR TREATMENT OF CORONARY ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERIES: IMPROVE-CED TRIAL

2021 ◽  
Vol 77 (18) ◽  
pp. 3409
Author(s):  
Michel Corban ◽  
Takumi Toya ◽  
Diana Albers ◽  
Faten Sebaali ◽  
John Bois ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Therapy ◽  
Coronary Arteries ◽  
Coronary Endothelial Dysfunction

Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression

2011 ◽  
Vol 300 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Julie Favre ◽  
Ji Gao ◽  
An Di Zhang ◽  
Isabelle Remy-Jouet ◽  
Antoine Ouvrard-Pascaud ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Coronary Endothelial Dysfunction

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.

Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction

2005 ◽  
Vol 289 (1) ◽  
pp. H48-H56 ◽  
Author(s):  
Jarrod D. Knudson ◽  
Ü. Deniz Dincer ◽  
Cuihua Zhang ◽  
Albert N. Swafford ◽  
Ryoji Koshida ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Coronary Arteries ◽  
Leptin Receptor ◽  
Receptor Protein ◽  
Zucker Rats ◽  
Pcr Analysis ◽  
Leptin Receptors ◽  
Coronary Endothelium ◽  
Coronary Endothelial Dysfunction

Obesity is associated with marked increases in plasma leptin concentration, and hyperleptinemia is an independent risk factor for coronary artery disease. As a result, the purpose of this investigation was to test the following hypotheses: 1) leptin receptors are expressed in coronary endothelial cells; and 2) hyperleptinemia induces coronary endothelial dysfunction. RT-PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium. Furthermore, immunocytochemistry demonstrated that the long-form leptin receptor protein (ObRb) is present in human coronary endothelium. The functional effects of leptin were determined using pressurized coronary arterioles (<130 μm) isolated from Wistar rats, Zucker rats, and mongrel dogs. Leptin induced pharmacological vasodilation that was abolished by denudation and the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester and was absent in obese Zucker rats. Intracoronary leptin dose-response experiments were conducted in anesthetized dogs. Normal and obese concentrations of leptin (0.1–3.0 μg/min ic) did not significantly change coronary blood flow or myocardial oxygen consumption; however, obese concentrations of leptin significantly attenuated the dilation to graded intracoronary doses of acetylcholine (0.3–30.0 μg/min). Additional experiments were performed in canine coronary rings, and relaxation to acetylcholine (6.25 nmol/l-6.25 μmol/l) was significantly attenuated by obese concentrations of leptin (625 pmol/l) but not by physiological concentrations of leptin (250 pmol/l). The major findings of this investigation were as follows: 1) the ObRb is present in coronary arteries and coupled to pharmacological, nitric oxide-dependent vasodilation; and 2) hyperleptinemia produces significant coronary endothelial dysfunction.

Selective right, but not left, coronary endothelial dysfunction precedes development of pulmonary hypertension and right heart hypertrophy in rats

2006 ◽  
Vol 290 (2) ◽  
pp. H758-H764 ◽  
Author(s):  
Xiaowei Sun ◽  
David D. Ku
Keyword(s):  
Pulmonary Hypertension ◽  
Methyl Ester ◽  
Endothelial Dysfunction ◽  
Coronary Arteries ◽  
Left Ventricular ◽  
Heart Hypertrophy ◽  
Right Heart ◽  
Marked Enhancement ◽  
Coronary Endothelial Dysfunction ◽  
Selective Impairment

We investigated a causal role for coronary endothelial dysfunction in development of monocrotaline (MCT)-induced pulmonary hypertension and right heart hypertrophy in rats. Significant increases in pulmonary pressure and right ventricular weight did not occur until 3 wk after 60 mg/kg MCT injection (34 ± 4 vs. 19 ± 2 mmHg and 37 ± 2 vs. 25 ± 1% septum + left ventricular weight in controls, respectively). Isolated right coronary arteries (RCA) showed significant decreases in acetylcholine-induced NO dilation in both 1-wk (33 ± 3% with 0.3 μM; n = 5) and 3-wk (18 ± 3%; n = 11) MCT rats compared with control rats (71 ± 8%, n = 10). Septal coronary arteries (SCA) showed a smaller decrease in acetylcholine dilation (55 ± 8% and 33 ± 7%, respectively, vs. 73 ± 8% in controls). No significant change was found in the left coronary arteries (LCA; 88 ± 6% and 81 ± 6%, respectively, vs. 87 ± 3% in controls). Nitro-l-arginine methyl ester-induced vasoconstriction, an estimate of spontaneous endothelial NO-mediated dilation, was not significantly altered in MCT-treated SCA or LCA but was increased in RCA after 1 wk of MCT (−41 ± 6%) and decreased after 3 wk (−18 ± 3% vs. −27 ± 3% in controls). A marked enhancement to 30 nM U-46619-induced constriction was also noted in RCA of 3-wk (−28 ± 6% vs. −9 ± 2% in controls) but not 1-wk (−12 ± 7%) MCT rats. Sodium nitroprusside-induced vasodilation was not different between control and MCT rats. Together, our findings show that a selective impairment of right, but not left, coronary endothelial function is associated with and precedes development of MCT-induced pulmonary hypertension and right heart hypertrophy in rats.

Abstract 1157: Coronary Endothelial Dysfunction In Mice With Conditional, Cardiomyocyte Specific Overexpression Of The Mineralocorticoid Receptor: Prevention By An Antioxidant Treatment

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Julie Favre ◽  
Andi Zhang ◽  
Christian Thuillez ◽  
Frèdèric Jaisser ◽  
Vincent Richard
Keyword(s):  
Vitamin E ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Antioxidant Treatment ◽  
No Donor ◽  
Doxycycline Treatment ◽  
Coronary Endothelial Dysfunction

Deleterious effects of aldosterone excess have been demonstrated in cardiovascular diseases, and they might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between aldosterone-mediated effects on the cardiomyocyte on one hand and the coronary arteries on the other hand are unknown. Thus, we used a mouse model of conditional, cardiomyocyte-specific overexpression of human mineralocorticoid receptor (MR) (Ouvrard-Pascaud et al., Circulation 2005) and observed its effects on coronary endothelial function. Three months old transgenic (TG) mice were obtained after removing doxycycline treatment used to inhibit lethal embryonic MR overexpression. TG mice and their matched controls (Cont) were either untreated or treated with MR antagonist canrenoate (40 mg/kg/day) or with an antioxidant treatment (vitamin E 1% in chow and vitamin C 0.05% in water) for 1 month. Segments of left coronary arteries (diameter 180 –220 μm) were isolated and mounted in a wire myograph. After pre-contraction with serotonin, we assessed endothelium-mediated (either NO-dependent or independent) relaxations in response to increasing concentrations of acetylcholine (Ach) before and after incubation with a NOSynthase inhibitor (LNNA). Compared to control mice, cardiac MR overexpression induced decreased relaxing responses to Ach either without (maximal relaxation: Cont: 95±4% n=7; TG: 68±8% n=7 p<0.05) or with LNNA (Cont: 19±3% n=7; TG: 5±4% n=7 p<0.05). A one month treatment by canrenoate totally prevented this coronary dysfunction which was also prevented by a one month treatment with vitamin E/vitamin C. The endothelium-independent relaxing responses to the NO-donor sodium nitroprusside were similar in all groups.We thus demonstrate that an increase in MR expression, restricted to cardiomyocytes is sufficient to induce a coronary endothelial dysfunction mostly through an increase in reactive oxygen species production. This suggests for the first time that the phenotypic changes induced by aldosterone within the cardiomyocyte are sufficient to induce per se a secondary coronary vascular dysfunction.

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