期刊
AMERICAN JOURNAL OF HYPERTENSION
卷 30, 期 8, 页码 756-764出版社
OXFORD UNIV PRESS
DOI: 10.1093/ajh/hpx027
关键词
angiotensin II type I receptor; autoimmunity; blood pressure; GPCR; hypertension; inflammatory cytokines; rennin-angiotensinaldosterone system; tissue transglutaminase; vascular stiffness
资金
- National Institutes of Health [1R01HL136969, 1R01HL113574, P01HL114457-01]
- UTHealth Pulmonary Center of Excellence
Inflammatory cytokines cause hypertension when introduced into animals. Additional evidence indicates that cytokines induce the production of autoantibodies that activate the AT1 angiotensin receptor (AT1R). Extensive evidence shows that these autoantibodies, termed AT1-AA, contribute to hypertension. We review here recent studies showing that cytokine-induced hypertension and AT1-AA production require the ubiquitous enzyme, tissue transglutaminase (TG2). We consider 3 mechanisms by which TG2 may contribute to hypertension. (i) One involves the posttranslational modification (PTM) of AT1Rs at a glutamine residue that is present in the epitope sequence (AFHYESQ) recognized by AT1-AA. (ii) Another mechanism by which TG2 may contribute to hypertension is by PTM of AT1Rs at glutamine 315. Modification at this glutamine prevents ubiquitination-dependent proteasome degradation and allows AT1Rs to accumulate. Increased AT1R abundance is likely to account for increased sensitivity to Ang II activation and in this way contribute to hypertension. (iii) The increased TG2 produced as a result of elevated inflammatory cytokines is likely to contribute to vascular stiffness by modification of intracellular contractile proteins or by crosslinking vascular proteins in the extracellular matrix. This process, termed inward remodeling, results in reduced vascular lumen, vascular stiffness, and increased blood pressure. Based on the literature reviewed here, we hypothesize that TG2 is an essential participant in cytokine-induced hypertension. From this perspective, selective TG2 inhibitors have the potential to be pharmacologic weapons in the fight against hypertension.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据