Influence of Neuropeptide Y and Neuropeptide Y 2 Receptor Variants in Acute Coronary Syndrome

Abstract Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (p<0.05). Results An association of NPY c.20T>C variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Role of neuropeptide Y2 receptor in neuropathic pain in rats / 中华麻醉学杂志

Objective To evaluate the role of neuropeptide Y2 receptor (NPY2R) in neuropathic pain (NP) in rats.Methods Thirty-six adult male Sprague-Dawley rats,aged 8 weeks,weighing 190-210 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),group NP and NPY2R antisense ohgonucleotide group (group ODN).NP was induced by chronic constrictive injury (CCI).5 μg/μl NPY2R antisense oligonucleotide 30 μl was injected intrathecally 7 days after CCI in group ODN.While normal saline 30 μl was injected intrathecally in group S.The mechanical paw withdrawal threshold and cold allodynia were measured 3 days before CCI (T0,baseline),7 days after CCI (T1) and at 15 min,1.5,3.0,4.5 and 6.0 h after intrathecal injection (T2-6).The animals were then sacrificed after the last measurement and the lumbar segment of spinal cord was removed for determination of the expression of NPY2R and calcitonin gene-related peptide (CGRP) and co-expression of NPY2R with CGRP in spinal dorsal horn neurons (by immuno fluoresceence).Results Compared with group S,the mechanical paw withdrawal threshold was significantly decreased and cold allodynia was increased at T1-6,and the expression of NPY2R and CGRP and co-expression of NPY2R with CGRP in spinal dorsal horn neurons was up-regulated in NP and ODN groups (P ＜ 0.05).Compared with group NP,the mechanical paw with-drawal threshold was significantly increased at T3-5,and the expression of NPY2R and co-expression of NPY2R with CGRP in spinal dorsal horn neurons was down-regulated (P ＜ 0.05),and no significant change was found in cold allodynia and the expression of CGRP in spinal dorsal horn neurons in ODN group (P ＞ 0.05).Conclusion NPY2R in the spinal cord dorsal horn is involved in the maintenance of mechanical hyperalgesia,but not in the maintenance of clod hyperalgesia in rats.

Expression of neuropeptide Y and its receptors in the cardinal ligaments and uterosacral ligaments in patients with pelvic organ prolapse / 中华妇产科杂志

Objective To evaluate the distribution of neuropeptide Y and its receptors in the cardinal ligament and uterosaeral ligaments in women with and without pelvic organ prolapse(POP).Methods Sixteen patients with pelvic organ prolapse entered the study.All patients were evaluated by pelvic organ prolapse quantitation(POP-Q).Group A consisted of six patients with grade Ⅰ,Ⅱ POP,and group B comprised ten patients with grade Ⅲ,Ⅳ POP.Eight nonfunctional ovarian tumor patients without POP were recruited as control subjects.Biopsies of cardinal ligament and uterosacral ligament were obtained from each woman during surgery.Immunohistochemical study with polyclonal antibody against a general nerve marker S-100 and neuropeptide Y was performed on paraffin-embedded sections of all the samples.In addition,mRNA levels of the human NPY-Y1 and NPY-Y2 receptors were assessed in both patients and controls.Results (1)NPY immunoreactivities were identified in both cardinal ligament and uterosacral ligament. NPY immunoreactive nerve fibers were insignificantly lower in POP patients(P＞0.05).The distribution pattern of NPY was similar in cardinal ligament and uterosacral ligament ( P＞0. 05 ). (2)mRNAs encoding the NPY-Y1 and NPY-Y2 receptors were detected in the pelvic supporting tissues. Besides the expected NPY-Y1 PCR products, an additional 97 bp long amplicon originating from an alternative splicing event was found in most tissues studied. (3)In cardinal ligaments, mRNA encoding NPY-Y1 receptor had a significant difference between group A(3.9±1.0)and B (6. 0±1.5), and between control (3.4±0.9) and group B (P = 0. 019,P = 0. 004), while there was no significant difference between group A and controls(P =0. 082). In uteresacral ligaments, mRNA encoding NPY-Y1 receptor had no significant difference between Group A(6. 0±1.1) and B (6. 3±0. 7), or between group A and controls(4. 8±0. 7;P = 0. 151 ,P = 0. 690);while there was a significant difference between group B and controls (P = 0. 016).(4) mRNA encoding NPY-Y2 receptor had no significant difference between controls (0. 49±0. 34, 0. 61±0. 15 ), group A (0. 56±0. 21,0. 67±0. 13) and group B (0. 85±0. 43, 0. 69±0. 21 ) patients in cardinal ligament and uterosacral ligaments ( P＞0. 05 ). (5) mRNA encoding NPY-Y1 ( P = 0. 084 ) and NPY-Y2 (P=0.470) receptors had no significant difference between cardinal ligament and uterosacral ligament.Conclusions There are NPY and NPY receptors in cardinal and uterosacral ligaments. The increased expression of NPY Y1 receptor may be related to local blood flow reduction and structural changes of pelvic supporting tissue.