Department of Physiology, Amsterdam UMC, Vrije Universiteit, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
Heart Rhythm. 2020 Jan;17(1):115-122. doi: 10.1016/j.hrthm.2019.07.010. Epub 2019 Jul 12.
Heat shock proteins (HSPs) are important chaperones that regulate the maintenance of healthy protein quality control in the cell. Impairment of HSPs is associated with aging-related neurodegenerative and cardiac diseases. Geranylgeranylacetone (GGA) is a compound well known to increase HSPs through activation of heat shock factor-1 (HSF1). GGA increases HSPs in various tissues, but whether GGA can increase HSP expression in human heart tissue is unknown.
The purpose of this study was to test whether oral GGA treatment increases HSP expression in the atrial appendages of patients undergoing cardiac surgery.
HSPB1, HSPA1, HSPD1, HSPA5, HSF1, and phosphorylated HSF1 levels were measured by western blot analysis in right and left atrial appendages (RAAs and LAAs, respectively) collected from patients undergoing coronary artery bypass grafting (CABG) who were treated with placebo (n = 13) or GGA 400 mg/da(n = 13) 3 days before surgery. Myofilament fractions were isolated from LAAs to determine the levels of HSPB1 and HSPA1 present in these fractions.
GGA treatment significantly increased HSPB1 and HSPA1 expression levels in RAA and LAA compared to the placebo group, whereas HSF1, phosphorylated HSF1, HSPD1, and HSPA5 were unchanged. In addition, GGA treatment significantly enhanced HSPB1 levels at the myofilaments compared to placebo.
Three days of GGA treatment is associated with higher HSPB1 and HSPA1 expression levels in RAA and LAA of patients undergoing CABG surgery and higher HSPB1 levels at the myofilaments. These findings pave the way to study the role of GGA as a protective compound against other cardiac diseases, including postoperative atrial fibrillation.
热休克蛋白（HSPs）是一种重要的伴侣蛋白，可调节细胞内健康蛋白质质量控制的维持。HSPs 的损伤与衰老相关的神经退行性和心脏疾病有关。金合欢基丙酮（GGA）是一种众所周知的化合物，可通过激活热休克因子-1（HSF1）增加 HSPs。GGA 可增加各种组织中的 HSPs，但 GGA 是否能增加人心组织中的 HSP 表达尚不清楚。
本研究旨在测试口服 GGA 治疗是否能增加接受心脏手术的患者心房附件中的 HSP 表达。
通过 Western blot 分析测量接受冠状动脉旁路移植术（CABG）的患者右心房附件（RAA）和左心房附件（LAA）中 HSPB1、HSPA1、HSPD1、HSPA5、HSF1 和磷酸化 HSF1 的水平，这些患者在手术前 3 天分别接受安慰剂（n=13）或 GGA 400mg/da（n=13）治疗。从 LAA 中分离肌丝分数，以确定这些分数中存在的 HSPB1 和 HSPA1 水平。
与安慰剂组相比，GGA 治疗显著增加了 RAA 和 LAA 中的 HSPB1 和 HSPA1 表达水平，而 HSF1、磷酸化 HSF1、HSPD1 和 HSPA5 则不变。此外，与安慰剂相比，GGA 治疗显著增强了肌丝中的 HSPB1 水平。
GGA 治疗 3 天与 CABG 手术患者的 RAA 和 LAA 中 HSPB1 和 HSPA1 表达水平升高以及肌丝中的 HSPB1 水平升高有关。这些发现为研究 GGA 作为一种预防其他心脏疾病（包括术后心房颤动）的保护化合物的作用铺平了道路。
