Delafontaine P
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cardiovasc Res. 1995 Dec;30(6):825-34.
A large body of evidence has conclusively shown that IGF I is an essential regulator of developmental growth. Thus mice bearing a null mutation for the IGF IR gene invariably die shortly after birth, and mice bearing a null mutation for the IGF I gene have a high neonatal mortality rate and marked growth retardation [158,159]. The ubiquitous effects of IGF I make it likely that this autocrine/endocrine system plays an important role in cardiovascular development. Its potential role in cardiovascular pathophysiology has raised considerable interest over the last several years. There is strong evidence that IGF I is a critical determinant of vascular growth responses in vitro and in vivo. Regulation of VSMC IGF IR availability appears to be crucial for the control of VSMC growth, and as such is at a convergence point for the effects of multiple growth factors. Clinical studies relating to IGF I in hypertension are extremely limited but significant data from animal studies now suggest a role for IGF I as a mediator of hypertrophic/hyperplastic responses in hypertension. Furthermore, significant animal data now exist implicating IGF I as an important mediator of cardiac hypertrophic responses. The development of a specific pharmacologic inhibitor of the IGF IR should allow rational clinical trials to address the function of IGF I as a mediator of cardiovascular growth responses. Specifically, areas of great interest will include the potential prevention of post-angioplasty restenosis, of atherosclerotic lesion development and progression, and of the complications of hypertensive vascular disease. The use of IGF I to ameliorate myocardial growth and function post infarction, to promote angiogenesis and collateral artery formation in the setting of peripheral vascular disease, are other important directions for future research. The use of IGF I to improve wound healing, improve recovery from acute renal failure and improve glucose control is currently under investigation. Clearly ongoing studies addressing the mechanisms whereby IGF I interacts with its receptor and binding proteins to produce its effects in cardiovascular tissues, will provide a rationale for novel and pertinent clinical research.
大量证据确凿地表明，胰岛素样生长因子I（IGF I）是发育性生长的重要调节因子。因此，胰岛素样生长因子I受体（IGF IR）基因发生无效突变的小鼠在出生后不久必然死亡，而胰岛素样生长因子I基因发生无效突变的小鼠新生儿死亡率高且有明显的生长迟缓[158,159]。IGF I的普遍作用表明，这种自分泌/内分泌系统在心血管发育中发挥重要作用。在过去几年中，其在心血管病理生理学中的潜在作用引起了相当大的关注。有强有力的证据表明，IGF I在体外和体内都是血管生长反应的关键决定因素。血管平滑肌细胞（VSMC）中IGF IR的可利用性调节似乎对VSMC生长的控制至关重要，因此处于多种生长因子作用的交汇点。与高血压中IGF I相关的临床研究极其有限，但来自动物研究的重要数据现在表明，IGF I在高血压中作为肥厚/增生反应的介质发挥作用。此外，现在有大量动物数据表明IGF I是心脏肥厚反应的重要介质。IGF IR特异性药理抑制剂的开发应能使合理的临床试验得以开展，以研究IGF I作为心血管生长反应介质的功能。具体而言，备受关注的领域将包括血管成形术后再狭窄、动脉粥样硬化病变发展和进展以及高血压血管疾病并发症的潜在预防。使用IGF I改善心肌梗死后的生长和功能、促进外周血管疾病情况下的血管生成和侧支动脉形成，是未来研究的其他重要方向。目前正在研究使用IGF I改善伤口愈合、促进急性肾衰竭恢复以及改善血糖控制。显然，正在进行的研究探讨IGF I与其受体和结合蛋白相互作用以在心血管组织中产生作用的机制，将为新颖且相关的临床研究提供理论依据。
