前列环素、动脉粥样硬化和糖尿病的生理和临床方面的考虑

Title:Prostacyclin, Atherothrombosis and Diabetes Mellitus: Physiologic and Clinical Considerations

Volume: 16 Issue: 4

Author(s): J. Stitham, J. Hwa

Affiliation:

关键词: 阿司匹林、动脉粥样硬化、糖尿病、前列环素、血栓素、前列环素受体。

摘要: Prostacyclin (PGI2) and other metabolites of arachidonic acid are increasingly recognized for their role in the pathophysiology of human disease. A growing body of evidence from randomized controlled trials, studies of human prostacyclin receptor (hIP) variants, and IP-receptor knockout studies in mice has shown that PGI₂ may have a protective effect on atherothrombotic risk. Increased risk of atherosclerosis and thrombotic sequelae may be attributed, in part, to downregulation of the prostacyclin pathway. Clinical studies with nonsteroidal antiinflammatory drugs (NSAIDs) that were selective for the cyclooxygenase-2 (COX-2) isoenzyme, although protective of mucosa in the gastrointestinal tract, first alluded to a potential role of PGI₂ in atherothrombotic risk. Outcomes from early clinical trials showed a 2- to 3-fold increase in risk of incurring a thrombotic event (e.g., myocardial infarction or stroke). Further analyses suggested that atherothrombotic risk is a continuous variable with relative NSAID COX-2 selectivity, and that the COX-2 metabolic product, PGI₂, appears to play a key role. Effects of reduced PGI₂ levels may be felt in particular by patients with diabetes mellitus, a patient population at the high end of the cardiovascular risk spectrum. Therapies that spare PGI₂ may provide the greatest level of protection. The mechanism of protection by PGI₂ is under intense investigation.

Cite this article as:

J. Stitham, J. Hwa , Prostacyclin, Atherothrombosis and Diabetes Mellitus: Physiologic and Clinical Considerations, Current Molecular Medicine 2016; 16 (4) . https://dx.doi.org/10.2174/1566524016666160316150728