Metabolic syndrome, today affecting more than 20% of the US population, is a group of 5 conditions that often coexist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here, we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo and blunts blood pressure elevation in response to a high-fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.

中文翻译：

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内皮脂滴抑制 eNOS 将高脂肪消耗与血压升高联系起来


目前，代谢综合征影响着超过 20% 的美国人口，它是一组经常同时存在的 5 种病症，极易引发心血管疾病。这些疾病之间的机制尚不清楚，尤其是其中两个：肥胖和血压升高。在这里，我们发现，小鼠的高脂肪消耗会导致整个生物体内皮细胞中脂滴的积累，并且内皮细胞中脂滴的积累会抑制内皮一氧化氮合酶（eNOS），减少一氧化氮的产生，升高血压，并加速动脉粥样硬化。从机制上讲，脂滴的积累会破坏 eNOS mRNA 的稳定性，并激活内皮炎症信号级联反应，从而抑制 eNOS 和 NO 的产生。药理学预防脂滴形成可以逆转细胞培养物和体内对 NO 产生的抑制，并抑制高脂肪饮食引起的血压升高。这些结果强调了脂滴作为内皮细胞生物学的一个关键且未被重视的组成部分，解释了脂质如何急剧升高血压，并为肥胖和血压升高之间的流行病学联系提供了机制解释。