Improvement In Coronary Endothelial Function Research Articles

Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol.

Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol.

0542 : Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In the present study, the role of MR expressed in vascular smooth muscle cells (VSMC) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MRSMKO) and mice treated with the MR antagonist finerenone (MIfine) had improved left ventricular (LV) compliance and elastance when compared to infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, ml/mg/min: MI-CTL: 1.1±0.5, NS; MIMRSMKO: 4.6±1.6, P<0.05; MI-fine: 3.6±0.7, P<0.01). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholineinduced NO-dependent relaxation, was also improved by MR deletion in VSMC or by finerenone treatment (relaxation %: MI-CTL: 36±5, MIMRSMKO: 54±3 and MI-fine: 76±4; P<0.05). Such impairment of the coronary endothelial function upon MI involved an oxidative-stress that was reduced when MR was deleted in VSMC or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from non-infarcted animals with low dose angiotensin-II (10-9mol/L) induced oxidative-stress and impaired acetylcholine-induced relaxation in CTL but neither in MRSMKO nor in mice pre-treated with finerenone. In conclusion, deletion of MR in VSMC improved LV dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects. The author hereby declares no conflict of interest

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, mL mg(-1) min(-1): MI-CTL: 1.1 ± 0.5, nonsignificant; MI-MR(SMKO): 4.6 ± 1.6 [P<0.05]; MI-fine: 3.6 ± 0.7 [P<0.01]). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholine-induced nitric oxide-dependent relaxation, was also improved by MR deletion in VSMCs or by finerenone treatment (relaxation %: MI-CTL: 36 ± 5, MI-MR(SMKO): 54 ± 3, and MI-fine: 76 ± 4; P<0.05). Such impairment of the coronary endothelial function on MI involved an oxidative stress that was reduced when MR was deleted in VSMCs or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from noninfarcted animals with low-dose angiotensin-II (10(-9) mol/L) induced oxidative stress and impaired acetylcholine-induced relaxation in CTL but neither in MR(SMKO) nor in mice pretreated with finerenone. In conclusion, deletion of MR in VSMCs improved left ventricular dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects.

The fate of large-diameter Dacron® vascular grafts in surgical practice: Are we really satisfied?

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Positive influence of aspirin on coronary endothelial function: Importance of the dose

To investigate the effects of different doses of aspirin on coronary endothelial function. The study included 139 Japanese subjects (mean age, 60 years; 53 women) with angiographically normal coronary arteries. Patients were distributed into Group I (n = 63), who was administered aspirin and Group II (n = 76), the control, who were not administered aspirin. Group I was further divided into Group Ia (n = 50, low-dose aspirin, 100 mg) and Group Ib (n = 13, high-dose aspirin, 500 mg). After a routine coronary angiography, acetylcholine (ACh; 3 and 30 μg/min successively) and nitroglycerin (NTG) were infused into the left coronary ostium over 2 min. The change in the diameter of the coronary artery in response to each drug was expressed as the percentage change from baseline values. The patient characteristics did not differ between the two groups. The change in coronary diameter in response to ACh was greater in Group I than in Group II (P = 0.0043), although the NTG-induced coronary vasodilation was similar between groups. ACh-induced dilation was greater in Group Ia than in Group Ib (P = 0.0231). Multivariate regression analysis showed that a low-dose of aspirin (P = 0.0004) was one of the factors associated with ACh-induced dilation at 30 μg/min. In subjects with angiographically normal coronary arteries, aspirin only had a positive influence on coronary endothelial function at the low dose of 100 mg. This improvement of coronary endothelial function may be involved in the preventive effect of aspirin against future coronary events.

Practical prevention of cardiac remodeling and atrial fibrillation with full-spectrum antioxidant therapy and ancillary strategies

A wealth of research data points to increased oxidative stress as a key driver of the cardiac remodeling triggered by chronic pressure overload, loss of functional myocardial tissue, or atrial fibrillation. Oxidative stress is a mediator of the cardiomyocyte hypertrophy and apoptosis, the cardiac fibrosis, and the deficits in cardiac function which typify this syndrome, and may play a role in initiating and sustaining atrial fibrillation. Nox2- and Nox4-dependent NADPH oxidase activity appears to be a major source of this oxidative stress, and oxidants can induce conformational changes in xanthine dehydrogenase, nitric oxide synthase, and the mitochondrial respiratory chain which increase their capacity to generate superoxide as well. Consistent with these insights, various synthetic antioxidants have been shown to suppress cardiac remodeling in rodents subjected to myocardial infarction, aortic constriction, or rapid atrial pacing. It may prove feasible to achieve comparable benefits in humans through use of a "full-spectrum antioxidant therapy" (FSAT) that features a complementary array of natural antioxidants. Spirulina is a rich source of phycocyanobilin, a derivative and homolog of biliverdin that appears to mimic the potent inhibitory impact of biliverdin and free bilirubin on NADPH oxidase activity. Mega-doses of folate can markedly increase intracellular levels of tetrahydrofolates which have potent and versatile radical-scavenging activities - including efficient quenching of peroxynitrite-derived radicals Supplemental coenzyme Q10, already shown to improve heart function in clinical congestive failure, can provide important antioxidant protection to mitochondria. Phase 2 inducer nutraceuticals such as lipoic acid, administered in conjunction with N-acetylcysteine, have the potential to blunt the impact of oxidative stress by boosting myocardial levels of glutathione. While taurine can function as an antioxidant for myeloperoxidase-derived radicals, its positive inotropic effect on the failing heart seems more likely to reflect an effect on intracellular calcium dynamics. These measures could aid control of cardiac modeling less directly by lowering elevated blood pressure, or by aiding the perfusion of ischemic cardiac regions through an improvement in coronary endothelial function. Since nitric oxide functions physiologically to oppose cardiomyocyte hypertrophy and cardiac fibrosis, and is also a key regulator of blood pressure and endothelial function, cocoa flavanols - which provoke endothelial release of nitric oxide - might usefully complement the antioxidant measures recommended here.

Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus

To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU). In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima-media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 +/- 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P < or = 0.036 and r = 0.46, P < or = 0.055) and with an improvement in endothelium-related DeltaMBF to CPT and to adenosine (r = 0.46, P < or = 0.038 and r = 0.36, P < or = 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in DeltaMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P < or = 0.001 by one-way analysis of variance). In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.

Long- but not short-term multifactorial intervention with focus on exercise training improves coronary endothelial dysfunction in diabetes mellitus type 2 and coronary artery disease

Patients with type 2 diabetes mellitus (T2DM) suffer from accelerated coronary artery disease. We assessed the effects of a multifactorial intervention with focus on exercise training on coronary endothelial function, vascular structure, and inflammation in serum and skeletal muscle biopsies, including mRNA expression of diabetes candidate genes. Twenty-three patients were randomized to either 4 weeks in-hospital exercise training (6 x 15 min bicycle/day, 5 days/week) and a hypocaloric diet, followed by a 5 months ambulatory program (30 min ergometer/day, 5 days/week, plus 1 h group exercise/week), or a control group. At the beginning of the study, at 4 weeks, and after 6 months changes in diameter of coronary arteries in response to acetylcholine and mean peak flow velocity were invasively measured; intramural plaques were assessed by intravascular ultrasound. Six months of intervention led to significant improvement of coronary endothelial function, whereas intramural plaque burden remained unchanged. After 4 weeks, endothelial function remained unchanged, however, lowest values for fasting glucose, HbA1c, high-sensitive C-reactive protein, total and LDL-cholesterol, and highest values for mRNA expression in skeletal muscle of p22, gp91, haem oxygenase 1, peroxisome proliferator activator receptor (PPAR) alpha and gamma were observed. There was a continuous increase for AdipoR1, AdipoR2, Glut4, interleukin-6, endothelial nitric oxide synthase, and PPARgamma-coactivator-1alpha mRNA expression in skeletal muscle. This is the first study to demonstrate improvement in coronary endothelial function by a multifactorial intervention which focused on exercise training in patients with T2DM. This coincided with improved markers of hyperglycaemia, insulin sensitivity, and inflammation both in serum and skeletal muscle biopsies.

Angiotensin II in the presence of an AT1 receptor blockade potentiates the coronary vasodilation mediated by bradykinin in the isolated rat heart

Our aim of this study was to explore the effect of Angiotensin II (Ang II) induced hypertension on coronary endothelial function in the presence of Ang II receptor blockade. Methods SD rats were continuously infused with Ang II (300 ng/kg/min, s.c.) via ALZET minipump for 14 days. Vehicle or telmisartan (10 mg/kg/day) was administered orally once daily. On day 14, coronary flow rate (CFR) in response to bradykinin (BK, 0.1 to 100 nM) was measured in a Langendorff-perfused isolated heart preparation. Results Mean arterial pressure (MAP) increased from 97±3 mmHg (day0) to 159±9 mmHg (day14) in the vehicle + Ang II group. Telmisartan prevented the Ang II-induced increase in MAP. CFR induced by BK was significantly reduced in the vehicle+Ang II group compared to that in normotensive rats, indicating an impaired endothelial response in the coronary arteries. In contrast, CFR changes to BK in the telmisartan-treated group were significantly higher than that in normotensive group, indicating an improvement in coronary endothelial function. Conclusion Ang II impaired coronary endothelial function, but in the presence of telmisartan improved coronary endothelial function above that of normotensive controls. The potentiation effect seen in telmisartan group most likely involves the actions of AII on AT2 receptors stimulation. *JF and LH contributed equally

Effect of Long-term Hormone Replacement Therapy on Coronary Endothelial Function in Postmenopausal Women

To determine the difference in endothelial function between premenopausal and postmenopausal women and to determine whether hormone replacement therapy (HRT) is associated with an improvement in coronary endothelial function. Women undergoing coronary physiology studies for chest pain at the Mayo Clinic In Rochester, Minn, between December 1992 and April 2002 underwent assessment of coronary endothelium-independent and -dependent function with intracoronary administration of adenosine and acetylcholine, respectively. The coronary diameters, coronary blood flows, and coronary velocity reserves were measured. A total of 270 women (89 premenopausal and 181 postmenopausal) participated in the study. Endothelium-dependent coronary blood flow change (baseline to peak flow) in response to acetylcholine (10(-4), 10(-5), and 10(-4) mol/L) was lower in postmenopausal women compared with premenopausal women (39.7% vs 72.9%, P = .03). There was no significant difference between the postmenopausal women receiving and not receiving HRT with regard to percent change in coronary diameter (-21.8% vs -13.9%, P = .15), percent change in coronary blood flow (37.3% vs 42.7%, P = .74), or coronary velocity reserve (2.7 vs 2.7, P = .82). This study shows that the postmenopausal state is associated with a greater abnormality in coronary endothelial function at the level of the microcirculation. Moreover, HRT status was not associated with an improvement in coronary endothelial function in postmenopausal women.

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine

The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine

ObjectivesThe purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. BackgroundEndothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. MethodsInvasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) ± L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. ResultsIn addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 ± 10% vs. 4 ± 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. ConclusionsWe conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary angiography. Our findings suggest that there are target populations in which supplementary L-arginine may be of therapeutic benefit in the amelioration of microvascular endothelial dysfunction. In view of the excess prevalence of cardiomyopathy among African Americans, pharmacologic correction of microcirculatory endothelial dysfunction in this group is an important area of further investigation and may ultimately prove to be clinically indicated.

Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs.

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-alpha levels, and O production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.

Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation

OBJECTIVESThis study was designed to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial function and cytokine activation in heart transplant recipients without angiographically detectable disease.BACKGROUNDCoronary endothelial dysfunction contributes to cardiac allograft vasculopathy. The vasoprotective effects of statins in heart transplant recipients may include restoration of endothelial function and suppression of allograft inflammatory activity.METHODSHeart transplant recipients (one to three years after heart transplant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequately controlled with simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately treated with simvastatin; and group 3 (n = 40), patients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]-α, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a prospective one-year follow-up study, changes in coronary endothelial function and cytokine levels were compared between 11 hypercholesterolemic patients treated with simvastatin and 9 controls.RESULTSEpicardial and microvascular endothelial functions were better in groups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-α gradients were significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05; TNF-α: p < 0.01). Plaque areas were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients treated with simvastatin, coronary endothelial function and cardiac cytokine activity significantly improved during the one-year follow-up.CONCLUSIONSInhibition of allograft inflammatory activity and attenuation of the coronary endothelial dysfunction observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy.

Relationship of gender, ethnicity, and risk factors to improvement in coronary endothelial function after intracoronary infusion of L-arginine

Relationship of gender, ethnicity, and risk factors to improvement in coronary endothelial function after intracoronary infusion of L-arginine