neuropeptide-y and Ventricular-Dysfunction--Left

Hypertension-induced left ventricular hypertrophy (LVH), along with ischemic heart disease, result in LV remodeling as part of a continuum that often leads to congestive heart failure. The neurohormonal model has been used to underpin many treatment strategies, but optimal outcomes have not been achieved. Neuropeptide Y (NPY) has emerged as an additional therapeutic target, ever since it was recognised as an important mediator released from sympathetic nerves in the heart, affecting coronary artery constriction and myocardial contraction. More recent interest has focused on the mitogenic and hypertrophic effects that are observed in endothelial and vascular smooth muscle cells, and cardiac myocytes. Of the six identified NPY receptor subtypes, Y(1), Y(2) and Y(5) appear to mediate the main functional responses in the heart. Plasma levels of NPY become elevated due to the increased sympathetic activation present in stress-related cardiac conditions. Also, NPY and Y receptor polymorphisms have been identified that may predispose individuals to increased risk of hypertension and cardiac complications. This review examines what understanding exists regarding the likely contribution of NPY to cardiac pathology. It appears that NPY may play a part in compensatory or detrimental remodeling of myocardial tissue subsequent to hemodynamic overload or myocardial infarction, and in angiogenic processes to regenerate myocardium after ischemic injury. However, greater mechanistic information is required in order to truly assess the potential for treatment of cardiac diseases using NPY-based drugs.

Topics: Animals; Heart Diseases; Humans; Neuropeptide Y; Ventricular Dysfunction, Left; Ventricular Remodeling

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

Diabetic cardiomyopathy was the most dangerous diabetic complication facing diabetics, with its exact mechanisms remaining obscure. Our study was conducted to investigate the expression of thrombospondin-1 (TSP-1) and neuropeptide Y (NPY) in myocardium of streptozotocin (STZ)-induced diabetic rats. We employed streptozotocin (STZ)-induced diabetic rats to study the alteration of the TSP-1 and NPY expression in the left ventricle myocardium in diabetic and normal group by immunohistochemistry and immunofluorescence. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before the animal model was induced. Four weeks after the induction of diabetes the weight of the diabeteic animals was 189.1+/-18.4 g, plasma glucose was 23.7+/-3.25 mmol/L and urine glucose was (++) to (+++); whereas the weight of the control animals was 260.5+/-32.1 g, plasma glucose was 4.9+/-0.5 mmol/L and urine glucose undetectable (-). The differences between the control and the diabetes group were distinct. A significant increase of the TSP-1 and NPY expression was also observed in the diabetic rat's heart. The number of the NPY positive myocardium and the light density of the positive myocardium in the left ventricle of the diabetic model were 17.3+/-2.1 and 102.5+/-9.3/mm(2), respectively, which were considered as increased when compared with the control that were 10.1+/-2.6 and 61.2+/-6.7, respectively. Our results support the view that high glucose conditions can induce an increased synthesis of TSP-1 through the PKC-TGF-beta-TSP-1 pathway, which in turn facilitate TGF-beta activation. Additionally, the activation of PKC may further lead to the over-expression of NPY. This may be involved in diabetic cardiomyopathy.

Topics: Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Disease Models, Animal; Disease Progression; Heart Ventricles; Immunohistochemistry; Myocardium; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Streptozocin; Thrombospondin 1; Ventricular Dysfunction, Left

Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients.. We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD.. NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P

Topics: Adult; Aged; Biomarkers; Cohort Studies; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Myocardium; Neuropeptide Y; Norepinephrine; Risk Factors; Ventricular Dysfunction, Left