neuropeptide-y and Coronary-Artery-Disease

With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease.

Topics: Coronary Artery Disease; Endothelial Cells; Humans; Muscle, Smooth, Vascular; Neuropeptide Y; Platelet Aggregation; Risk Factors

To explore possible differential effects between metoprolol and atenolol in patients with coronary artery disease.. The study was randomized, double blind, two-way crossover with the Y1 antagonist AR-H040922 given as IV infusion for 2 h or placebo. Most patients were treated with metoprolol or atenolol. In a post hoc analysis we compared the hemodynamic response to exercise of the Y1 antagonist in patients on metoprolol (n = 16) and atenolol (n = 5), and assessed respiratory sinus arrhythmia (RSA), an indirect measurement of cardiac vagal activation, in the placebo phase in patients on metoprolol (n = 26) and on atenolol (n = 24).. 1) The Y1 antagonist reduced the systolic blood pressure rise during and after exercise during atenolol, but not during metoprolol, while heart rate and maximal load were similar with the two beta-blockers and not affected by the Y1 antagonist. 2) At equal heart- and respiration-rate 7-8 min after exercise the RSA was significantly lower in atenolol than in metoprolol patients, while no difference was seen at rest before exercise.. These findings from this hypothesis generating study indicate that peripheral effects of NPY contribute less to cardiovascular stress reactions in patients on metoprolol than in those on atenolol.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aged; Angina, Stable; Atenolol; Blood Pressure; Coronary Artery Disease; Double-Blind Method; Exercise; Heart Rate; Humans; Male; Metoprolol; Middle Aged; Neuropeptide Y

There have been few epidemiological studies that have investigated genetic susceptibility to cardiovascular risk associated with the prevalence of metabolic syndrome (MetS). Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). Therefore, the aim of this study was to investigate the association between the NPY gene rs16147 polymorphism and the presence of MetS in a well defined group of Iranian subjects with angiographically-defined CAD.. A cross-sectional study design was used in which a total of 364 patients were recruited; 143 patients with MetS and 221 without MetS were genotyped using the ARMS-PCR technique. Logistic regression analyses were performed to determine the odds ratios (ORs) for the association of specific genotypes with the presence of MetS and related phenotypes.. The frequency of the variant G allele of the NPY gene was significantly higher in CAD patients without MetS (p = 0.032). Compared to the AA genotype of the NPY gene, individuals carrying the GG genotype had a reduced risk of MetS (OR = 0.51, 95% CI = 0.27-0.95, p = 0.034).. The rs16147 polymorphism may be associated with presence of MetS among subjects with documented CAD. Carriage of NPY A allele in patients with CAD is associated with a higher prevalence of MetS.

Topics: Adolescent; Adult; Aged; Coronary Artery Disease; Cross-Sectional Studies; Female; Genetic Predisposition to Disease; Humans; Iran; Male; Metabolic Syndrome; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; Prevalence; Risk Factors; Young Adult

Several genetic factors have been identified that may contribute to the risk of coronary artery disease (CAD). Variants of the neuropeptide Y (NPY) gene, whose products play an important role in regulating several physiological functions, have been associated with the risk of CAD in some populations. The purpose of this study was to investigate the relationship between the NPY gene rs16147 polymorphism and the presence of CAD in an Iranian population.. DNA samples of 922 subjects, including 433 with angiographically defined CAD (CAD+), 196 without angiographically defined significant CAD (CAD-) and 293 controls, were genotyped using polymerase chain reaction based on the amplification-refractory mutation system. Logistic regression analyses were performed to assess the association of rs16147 genotypes with the presence of significant CAD.. Although logistic regression analysis indicated that the NPY polymorphism rs16147 was nominally associated with an increased risk of CAD (p < 0.05), after adjustment for confounding factors, there was no evidence for any significantly increased or decreased risk of CAD with this polymorphism. However, in stratified analyses, the C allele was significantly associated with a reduced risk of CAD in males and subjects who were <50 years of age.. This study suggests that the rs16147 polymorphism in the NPY gene may not be a potential contributor to the risk of CAD in an Iranian population.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; Iran; Male; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; White People

The metabolic syndrome (MetS) is characterized by constellation of clinical and biochemical features that increase the risk of cardiovascular disease. Neuropeptide Y (NPY) is a neurotransmitter and enhances the development of obesity and other aspects of MetS. We determined the association between NPY Leu7Pro polymorphism and features of MetS in Iranian patients with coronary artery disease (CAD). A total of 550 patients with CAD including individuals with (n = 184) and without MetS (n = 366) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. A significantly higher frequency of the Leu7Pro polymorphism was found in patients with MetS compared with the non-MetS patients (P = .001). Furthermore, there was a significant difference in Pro7 frequency between diabetics versus nondiabetics (P = .005), dyslipidemic versus nondyslipidemic (P = .04), and obese versus nonobese (P = .001) in this population. Leu7Pro polymorphism is associated with the MetS in patients with CAD.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Coronary Artery Disease; Cross-Sectional Studies; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Metabolic Syndrome; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; Risk Factors

Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous systems as well as in the heart. A relationship has been reported between NPY gene variants and coronary artery disease (CAD) in some populations. However, there are few data on the NPY gene polymorphism and CAD in the Persian population. In the current study we have investigated the relationship between the NPY Leu7Pro polymorphism and CAD within a population from Iran.. A total of 1061 subjects were recruited; 609 patients and 452 healthy subjects. Four hundred and twenty eight of the patients had >50% stenosis; with the remaining 181 patients having <50% stenosis based on angiography. Angiography positive patients were divided into three groups: those with single (n=115), double (n=140), and triple vessel (n=173) disease. DNA analysis for the Leu7Pro polymorphism was performed using a PCR-RFLP technique.. A significantly higher frequency of the Leu7Pro genotype was observed in CAD patients compared with the control group (P<0.05). Patients with the Pro7 had significantly higher values for weight (P=0.027), BMI (P=0.001), hip circumference (P=0.003) and prevalence of diabetes mellitus (P=0.018) but reduced prevalence of a history of myocardial infarction (P=0.017).. The frequency of Leu7Pro polymorphism of NPY was 5.9% in our Iranian population; higher than reported for other Asian populations. The Leu7Pro polymorphism was associated with CAD in an Iranian population.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Case-Control Studies; Coronary Artery Disease; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetics, Population; Humans; Iran; Leucine; Male; Middle Aged; Neuropeptide Y; Polymorphism, Single Nucleotide; Prevalence; Proline; Young Adult

Neuropeptide Y (NPY) has a single nucleotide polymorphism at T1128C, leading to change of Leucine7 to Proline7. The Leu7Pro substitution has been linked to cardiovascular disease, but it is unknown whether the Pro7 allele is associated with increased or decreased risk of coronary heart disease (CHD). The aim of the present study was to investigate the association of the Leu7Pro polymorphism with coronary atherosclerosis and its consequences.. We studied two autopsy series comprising 700 unselected middle-aged Caucasian men (Helsinki Sudden Death Study) who had died suddenly out of hospital. Areas of coronary artery atherosclerosis, narrowings of coronary arteries, and presence of myocardial infarction and/or coronary thrombosis were analyzed. All information including CHD risk factor data was obtained from 410 men.. NPY genotype distribution was Leu7/Leu7=89.8%, Leu7/Pro7=10.0% and Pro7/Pro7=0.2%). Although the Pro7 allele was associated with reported hypertension (p=0.03), the men carrying Pro7 allele had lower area of fatty streaks (p=0.04), fibrotic lesions (p=0.07) and complicated lesions (p=0.004) in the left anterior descending (LAD) coronary artery and also less severe LAD narrowings (p=0.04) than men with the Leu7/Leu7 genotype. Supporting a protective role for the Pro7 allele against atherosclerosis, only 1 out of 46 men (2%) with coronary thrombosis carried the Pro7 allele (p=0.08 compared to men dying of other causes). This association weakened (OR 0.18 for Pro7 versus Leu7/Leu7, p=0.16) when adjusted for all available CHD risk factors.. NPY Pro7 substitution protects middle-aged men from coronary artery atherosclerosis and might decrease the risk of acute coronary events.

Topics: Adult; Aged; Autopsy; Coronary Artery Disease; Gene Expression Regulation; Genotype; Humans; Leucine; Male; Middle Aged; Neuropeptide Y; Polymorphism, Genetic; Proline; Protein Sorting Signals; Risk