Susic Dinko, Varagic Jasmina, Ahn Jwari, Frohlich Edward D
Hypertension Research Laboratory, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
Curr Drug Targets Cardiovasc Haematol Disord. 2004 Mar;4(1):97-101. doi: 10.2174/1568006043481347.
Aging, diabetes, and hypertension are conditions in which arterial and myocardial stiffness is increased. Increased arterial stiffness is manifested by an increased systolic arterial pressure, pulse pressure and pulse wave velocity, whereas increased myocardial stiffness is manifested by impaired left ventricular diastolic filling. Moreover, increased arterial stiffness increases cardiac workload, further aggravating already existing adverse changes in left ventricular structure and function. Indeed, studies in human beings have clearly shown that increased cardiovascular stiffness is a reliable predictor of cardiovascular morbidity and mortality. Increased cardiovascular stiffness is usually attributed to the development of fibrosis (i.e., accumulation of collagen). It has also been recognized that the increased cardiac and vascular stiffness may be due to increased collagen cross-linking due to the formation of advanced glycosylation end-products (AGEs). In agreement with this notion is the finding that an inhibitor of AGEs formation improves vascular stiffness in diabetic rats. More recently, cross-link breakers have been developed, and the beneficial effects of one such agent (ALT-711) have been shown in experimental and clinical settings. This report briefly summarizes age related changes in cardiovascular structure and function and describes results of experimental and clinical studies involving collagen cross-link breakers.
衰老、糖尿病和高血压是动脉和心肌僵硬度增加的病症。动脉僵硬度增加表现为收缩期动脉压、脉压和脉搏波速度增加，而心肌僵硬度增加表现为左心室舒张期充盈受损。此外，动脉僵硬度增加会增加心脏负荷，进一步加重左心室结构和功能已有的不良变化。事实上，对人类的研究清楚地表明，心血管僵硬度增加是心血管发病率和死亡率的可靠预测指标。心血管僵硬度增加通常归因于纤维化的发展（即胶原蛋白的积累）。人们还认识到，心脏和血管僵硬度增加可能是由于晚期糖基化终产物（AGEs）形成导致的胶原蛋白交联增加。与这一观点一致的是，AGEs形成抑制剂可改善糖尿病大鼠的血管僵硬度这一发现。最近，交联破坏剂已被开发出来，并且在实验和临床环境中已显示出一种此类药物（ALT - 711）的有益效果。本报告简要总结了心血管结构和功能的年龄相关变化，并描述了涉及胶原蛋白交联破坏剂的实验和临床研究结果。
