Institut Pasteur Korea, Bundang-gu, Gyeonggi-do, Korea.
Nat Rev Cardiol. 2010 Jan;7(1):22-9. doi: 10.1038/nrcardio.2009.224. Epub 2009 Dec 1.
A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects.
大量的研究,包括临床和动物模型研究以及体外分析,都对瘦素的心血管效应产生了浓厚的兴趣。因此,许多研究都探讨了瘦素在心力衰竭中心脏重构中的作用,以及瘦素对代谢、细胞凋亡、细胞外基质重构和肥大的影响是否可以解释所谓的肥胖悖论。此外,肥胖和高瘦素血症通常与高血压有关,并且已经证明了瘦素对贡献者(如动脉粥样硬化、内皮功能障碍和血栓形成)的交感神经张力调节或直接作用。不幸的是,将体外或动物模型中的基础研究转化为人体生理学证明是困难的。肥胖患者的瘦素抵抗程度是一个需要解决的有趣问题。此外,还必须进一步研究来自心脏和血管周围脂肪组织的瘦素的自分泌和旁分泌作用。精心计划和执行的研究对于确定瘦素在正常和疾病状态下对心血管系统的明确影响至关重要,这将是利用瘦素相关作用的任何治疗潜力的关键。