Department of Medical and Surgical Sciences, University of Catanzaro Magna Graecia, Viale Europa, località Germaneto 88100 Catanzaro, Italy.
Curr Pharm Des. 2014;20(4):609-15. doi: 10.2174/13816128113199990016.
Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their bioavailability, through complex mechanisms that have not been completely clarified yet. Here we first review clinical evidence suggesting not only that the circulatory levels of CRP and leptin show an independent correlation, but also that assessing them in tandem may result in an increased ability to predict cardiovascular disease. We summarize also molecular studies showing that leptin is able to promote CRP production from hepatocytes and endothelial cells in vitro and discuss the studies addressing the possibility that in vivo leptin administration may be able to modulate plasma CRP levels. Furthermore, we describe two studies demonstrating that CRP directly binds leptin in extra-cellular settings, thus impairing its biological actions. Finally we report genetic evidence that common variations at the leptin receptor locus are associated with CRP blood levels. Overall, the data reviewed here show that the chronic elevation of CRP observed in obese subjects may worsen leptin resistance, contributing to the pathogenesis of cardiovascular disease, and highlight a potential link between conditions, such as leptin resistance and endothelial dysfunction, that may be amenable of pharmacological treatment targeted to the disruption of leptin-CRP interaction.
已有研究报道，在肥胖等多种情况下，血浆中瘦素和 C 反应蛋白（CRP）的水平均会升高，并且与心血管病理生理过程和心血管风险增加有关；有趣的是，这两种生物标志物似乎能够通过尚未完全阐明的复杂机制相互调节其生物利用度。在此，我们首先综述了临床证据，这些证据不仅表明 CRP 和瘦素的循环水平呈独立相关性，而且还表明同时评估它们可能会提高预测心血管疾病的能力。我们还总结了一些分子研究，这些研究表明瘦素能够在体外促进肝细胞和内皮细胞中 CRP 的产生，并讨论了研究人员探讨了体内给予瘦素是否能够调节 CRP 水平的可能性。此外，我们还描述了两项研究，表明 CRP 在细胞外环境中能够直接结合瘦素，从而使其生物活性受到损害。最后，我们报告了遗传证据，证明瘦素受体基因座的常见变异与 CRP 血液水平有关。总的来说，本文综述的研究结果表明，肥胖患者中观察到的 CRP 慢性升高可能会加重瘦素抵抗，从而导致心血管疾病的发生，并强调了一些情况（如瘦素抵抗和内皮功能障碍）之间的潜在联系，这些情况可能可以通过针对破坏瘦素-CRP 相互作用的药物治疗来改善。
