neuropeptide-y and Coronary-Stenosis

The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature.. Peripheral venous NPY levels were significantly higher in patients with STEMI (n = 45) compared to acute coronary syndromes/stable angina ( n = 48) or with normal coronary arteries (NC, n = 16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r = 0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100-250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1 receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors.. High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1 receptor, and antagonists may be a useful PPCI adjunct therapy.

Topics: Acute Coronary Syndrome; Aged; Animals; Blood Flow Velocity; Case-Control Studies; Constriction; Coronary Sinus; Coronary Stenosis; Coronary Vessels; Edema; Female; Humans; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Myocardium; Neuropeptide Y; Percutaneous Coronary Intervention; Rats; ST Elevation Myocardial Infarction; Stroke Volume; Vascular Resistance; Ventricular Dysfunction, Left

Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to promote angiogenesis in in-vitro models. The aim of this study was to evaluate the relationship of plasma NPY levels with coronary collateral vessel development in patients with coronary artery disease.. The study included 81 patients with at least one coronary stenosis with at least 80% narrowing in coronary angiography. Collateral vessels were graded according to the Rentrop classification. The study patients were divided into two groups, namely patients with well-developed collaterals and patients with poorly developed collaterals. Well-developed collaterals were defined as Rentrop collateral score of at least 2. Plasma levels of NPY, vascular endothelial growth factor, fibroblast growth factor, and noradrenaline were measured using an enzyme-linked immunosorbent assay.. Plasma NPY was significantly higher in patients with well-developed collaterals as compared with patients with poorly developed collaterals (P=0.026). In contrast, plasma noradrenaline was significantly lower in patients with well-developed collaterals (P=0.022). There was no statistically significant difference in vascular endothelial growth factor and fibroblast growth factor levels between groups. The NPY level was positively correlated with the presence of diabetes (r=0.528, P<0.001). The extent of coronary artery disease (Gensini score) was significantly higher in patients with well-developed collaterals (P<0.001). After confounding variables were controlled for, the NPY level in patients with well-developed collaterals was significantly higher than those patients with poorly developed collaterals.. In this study, NPY levels were found to be significantly higher in patients with well-developed coronary collaterals compared with patients with poorly developed collaterals. New studies are needed to show whether this relationship is causal.

Topics: Aged; Biomarkers; Collateral Circulation; Coronary Angiography; Coronary Circulation; Coronary Stenosis; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factors; Humans; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Prospective Studies; Severity of Illness Index; Vascular Endothelial Growth Factor A

The primary purpose of this investigation was to determine whether ApoE(-/-) mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE(-/-) mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

Topics: Animals; Atherosclerosis; Blood Pressure; Cholesterol; Coronary Stenosis; Corticosterone; Disease Models, Animal; Hemorrhage; Humans; Inflammation; Mice; Mice, Inbred C57BL; Necrosis; Neovascularization, Pathologic; Neuropeptide Y; Plaque, Atherosclerotic; Stress, Psychological