Department of Systems Pharmacology and Translational Therapeutics (E.R., G.A.F.), University of Pennsylvania Perelman School of Medicine, Philadelphia.
Institute for Translational Medicine and Therapeutics (E.R., G.A.F.), University of Pennsylvania Perelman School of Medicine, Philadelphia.
Arterioscler Thromb Vasc Biol. 2024 Mar;44(3):558-583. doi: 10.1161/ATVBAHA.123.320045. Epub 2024 Jan 25.
Prostanoids are biologically active lipids generated from arachidonic acid by the action of the COX (cyclooxygenase) isozymes. NSAIDs, which reduce the biosynthesis of prostanoids by inhibiting COX activity, are effective anti-inflammatory, antipyretic, and analgesic drugs. However, their use is limited by cardiovascular adverse effects, including myocardial infarction, stroke, hypertension, and heart failure. While it is well established that NSAIDs increase the risk of atherothrombotic events and hypertension by suppressing vasoprotective prostanoids, less is known about the link between NSAIDs and heart failure risk. Current evidence indicates that NSAIDs may increase the risk for heart failure by promoting adverse myocardial and vascular remodeling. Indeed, prostanoids play an important role in modulating structural and functional changes occurring in the myocardium and in the vasculature in response to physiological and pathological stimuli. This review will summarize current knowledge of the role of the different prostanoids in myocardial and vascular remodeling and explore how maladaptive remodeling can be counteracted by targeting specific prostanoids.
前列腺素是由花生四烯酸经环氧化酶(COX)同工酶作用生成的具有生物活性的脂质。非甾体抗炎药(NSAIDs)通过抑制 COX 活性减少前列腺素的生物合成,是有效的抗炎、解热和镇痛药。然而,它们的使用受到心血管不良事件的限制,包括心肌梗死、中风、高血压和心力衰竭。虽然已经明确 NSAIDs 通过抑制血管保护前列腺素增加动脉粥样硬化血栓形成事件和高血压的风险,但关于 NSAIDs 与心力衰竭风险之间的联系知之甚少。目前的证据表明,NSAIDs 可能通过促进不良的心肌和血管重塑增加心力衰竭的风险。事实上,前列腺素在调节心肌和血管对生理和病理刺激发生的结构和功能变化方面发挥着重要作用。这篇综述将总结不同前列腺素在心肌和血管重塑中的作用,并探讨如何通过靶向特定前列腺素来对抗适应性重塑。