Department of Cardiology, Peking University People's Hospital, Beijing, China.
Chin Med J (Engl). 2013;126(11):2157-62.
Catestatin, a chromogranin A-derived peptide, is a potent antagonist of nicotine-evoked catecholamine release. We know that catecholamine plays an important role in cardiovascular remodeling induced by hypertension, therefore we hypothesized that catestatin would affect target-organ structure during hypertension.
Twelve spontaneously hypertensive rats (SHRs) were randomized to SHR control group and catestatin group, the normal control group was comprised of six healthy Wistar-Kyoto rats of the same age. Tail-cuff blood pressure and pulse rate were obtained at weeks 1, 4 and 8. At the end of the eight-week period, the heart, abdominal aorta and left kidney were excised and weighed, VG staining was done and the intima-media thickness of vessels and the collagen volume fraction were assessed by an image acquisition and analysis system. The proliferating cell nuclear antigen (PCNA) was observed by immunohistochemistry, and real time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of proliferative genes including cyclin A, ki67 and PCNA in the abdominal aorta.
All the parameters in SHR observed in the present study increased significantly compared to Wistar Kyoto rats (P < 0.01). With intervention with catestatin, the systolic blood pressure decreased slightly but it was not significantly different from the SHR control, the cardiac mass index and left ventricular mass index both decreased significant ly, the collagen volume fraction decreased by nearly 30% in the heart, by 25% in vessels and by 10% in the kidney, and the intima-media thickness and expression of proliferative genes, including cyclin A, ki67 and PCNA, in the abdominal aorta also decreased significant ly.
The present study indicated that catestatin could ameliorate proliferating changes of heart, kidney and vessels during hypertension, especially to the deposition of interstitial collagen. Blood pressure was not the main factor to mediate this effect, which suggested that catestatin could become a novel protective factor for hypertensive target organs.
Catestatin 是一种源自嗜铬粒蛋白 A 的肽，是一种有效的烟碱诱发儿茶酚胺释放的拮抗剂。我们知道儿茶酚胺在高血压引起的心血管重构中起着重要作用，因此我们假设 catestatin 会影响高血压期间的靶器官结构。
将 12 只自发性高血压大鼠（SHR）随机分为 SHR 对照组和 catestatin 组，正常对照组由 6 只同龄的健康 Wistar-Kyoto 大鼠组成。在第 1、4 和 8 周时测量尾袖血压和脉搏率。在 8 周结束时，取出心脏、腹主动脉和左肾并称重，进行 VG 染色，并通过图像采集和分析系统评估血管的内膜-中膜厚度和胶原容积分数。通过免疫组织化学观察增殖细胞核抗原（PCNA）的表达，并通过实时逆转录-聚合酶链反应（RT-PCR）检测腹主动脉中增殖基因（包括细胞周期蛋白 A、ki67 和 PCNA）的 mRNA 水平。
与 Wistar Kyoto 大鼠相比，本研究中观察到的所有 SHR 参数均显著增加（P < 0.01）。用 catestatin 干预后，收缩压略有下降，但与 SHR 对照组无显著差异，心脏质量指数和左心室质量指数均显著下降，心脏胶原容积分数下降近 30%，血管下降 25%，肾脏下降 10%，腹主动脉中增殖基因（包括细胞周期蛋白 A、ki67 和 PCNA）的内膜-中膜厚度和表达也显著下降。
本研究表明，catestatin 可改善高血压期间心脏、肾脏和血管的增殖变化，特别是对间质胶原的沉积。血压不是介导这种效应的主要因素，这表明 catestatin 可能成为高血压靶器官的一种新的保护因子。
