Dworatzek Elke, Baczko Istvan, Kararigas Georgios
Institute of Gender in Medicine and Center for Cardiovascular Research, Charite University Hospital, Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), Berlin Partner Site, Berlin, Germany.
Proteomics Clin Appl. 2016 Jan;10(1):84-91. doi: 10.1002/prca.201500031. Epub 2015 Sep 25.
Aging has severe implications for tissue damage and is a major risk factor for disease. However, the effects of aging on cardiac extracellular matrix (ECM) components in individuals free of cardiovascular disease are incompletely understood. We aimed at the characterization of the effects of aging on major ECM proteins in the heart of men and women.
Left ventricular (LV) samples of nondiseased human hearts technically unusable for transplantation obtained from general organ donors (n = 31; age 17-68 years; 48% women) were used for protein isolation. We separated the group into 17-40 years (n = 7 men and 7 women) and 50-68 years (n = 9 men and 8 women).
Analysis of ECM proteins demonstrated an age-dependent sex-specific regulation of collagen type I and III (interaction p < 0.05), type VI (interaction p = 0.01), tissue inhibitor of metalloproteinase 3 (interaction p < 0.05), SMAD2 (interaction p < 0.05), and SMAD3 (interaction p = 0.001). Overall, the levels of these proteins in younger individuals were lower in women than men, while in older individuals they were higher in women than men.
This age-mediated myocardial ECM remodeling might play a key role in the limited ability of the aging heart to adapt adequately to altered work load and to respond to tissue damage. Therapeutic agents that target ECM homeostasis represent promising prevention strategies.
衰老对组织损伤有严重影响，是疾病的主要危险因素。然而，衰老对无心血管疾病个体心脏细胞外基质（ECM）成分的影响尚未完全明确。我们旨在表征衰老对男性和女性心脏主要ECM蛋白的影响。
从一般器官捐赠者处获取的因技术原因无法用于移植的非病变人类心脏左心室（LV）样本（n = 31；年龄17 - 68岁；48%为女性）用于蛋白质分离。我们将该组分为17 - 40岁组（n = 7名男性和7名女性）和50 - 68岁组（n = 9名男性和8名女性）。
ECM蛋白分析显示，I型和III型胶原蛋白（交互作用p < 0.05）、VI型胶原蛋白（交互作用p = 0.01）、金属蛋白酶组织抑制剂3（交互作用p < 0.05）、SMAD2（交互作用p < 0.05）和SMAD3（交互作用p = 0.001）存在年龄依赖性的性别特异性调节。总体而言，这些蛋白在年轻个体中女性低于男性，而在老年个体中女性高于男性。
这种年龄介导的心肌ECM重塑可能在衰老心脏适应工作负荷改变和应对组织损伤的能力受限中起关键作用。针对ECM稳态的治疗药物代表了有前景的预防策略。
