1 Department of Molecular Biology, Instituto Nacional de Cardiología, Mexico City, Mexico.
2 Department of Pathology, Instituto Nacional de Cardiología, Mexico City, Mexico.
J Cardiovasc Pharmacol Ther. 2019 Nov;24(6):559-566. doi: 10.1177/1074248419838517. Epub 2019 May 5.
Statins may precipitate the onset of type 2 diabetes (T2D) in high-risk patients. In contrast, only the subset of individuals with insulin resistance and/or diabetes receives cardiovascular benefits with fibrates. In this context, previous observations from our laboratory suggested that atorvastatin induced an increase in visceral adipose tissue (VAT), whereas fenofibrate had the opposite effects in rabbits. Therefore, we determined the mass, morphology, and vascularization of VAT in New Zealand white rabbits (n = 6/group) that received 0.33 or 2.6 mg/kg/d of atorvastatin or fenofibrate, respectively, during 2 months. As expected, the cholesterol from the atorvastatin group was lower after treatment, while triglycerides decreased in the fenofibrate group. The mass of VAT from the fenofibrate group was 46% lower compared to the controls, meanwhile atorvastatin was associated with a larger diameter of adipocytes (+65%) than that of the control and fenofibrate groups. Fibroblast growth factor 2 () gene expression was lower in the fenofibrate group than in the control group (-54%). By contrast, vascular endothelial growth factor A (VEGF-A) gene expression in fenofibrate-treated rabbits was 110% higher than in the control group. In agreement with the gene expression, the marker of angiogenesis platelet endothelial cell adhesion molecule 1 was slightly but significantly higher (+10%) in rabbits treated with fenofibrate than in controls, as determined by immunohistochemistry. These results suggest that fenofibrate is associated with a favorable remodeling of VAT, that is, reduced mass and increased vascularization in normolipemic rabbits; in contrast, atorvastatin induced a nonfavorable remodeling of VAT. These results may be related to the cardiovascular benefits of fenofibrate and the increased risk of T2D in high-risk patients induced by atorvastatin.
他汀类药物可能会使高危患者发生 2 型糖尿病（T2D）。相比之下，只有胰岛素抵抗和/或糖尿病的个体才能从贝特类药物中获益。在这种情况下，我们实验室之前的观察结果表明，阿托伐他汀会导致内脏脂肪组织（VAT）增加，而非诺贝特则会产生相反的效果。因此，我们在新西兰白兔（n = 6/组）中确定了分别接受 0.33 或 2.6 mg/kg/d 的阿托伐他汀或非诺贝特治疗 2 个月后的 VAT 质量、形态和血管化。正如预期的那样，阿托伐他汀组的胆固醇在治疗后降低，而非诺贝特组的甘油三酯降低。与对照组相比，非诺贝特组的 VAT 质量降低了 46%，而阿托伐他汀组的脂肪细胞直径增大了 65%（比对照组和非诺贝特组都大）。与对照组相比，非诺贝特组的成纤维细胞生长因子 2（）基因表达降低了 54%。相比之下，非诺贝特组的血管内皮生长因子 A（VEGF-A）基因表达比对照组高 110%。与基因表达一致，用免疫组织化学法检测到，与对照组相比，用非诺贝特治疗的兔子中血管生成标志物血小板内皮细胞黏附分子 1 略有但显著升高（升高 10%）。这些结果表明，非诺贝特与 VAT 的有利重塑有关，即在正常血脂的兔子中减少质量和增加血管化；相比之下，阿托伐他汀会引起 VAT 的不利重塑。这些结果可能与非诺贝特的心血管益处以及阿托伐他汀在高危患者中引起的 2 型糖尿病风险增加有关。
