摘要：
Abdominal aortic aneurysms (AAA) are permanent and irreversible local dilatations of the abdominal aortic wall. Recent data indicate that the transforming growth factor-beta (TGF-beta) signaling pathway exerts a protective effect on the development of AAA. Some dysregulated microRNAs (miRNA) also appear involved in the expansion of AAA and miRNA-based therapeutics have been shown to effectively inhibit this process. New evidence has revealed that TGF-beta signaling and miRNA interaction may of physiologic and pathophysiologic significance including the progression of AAA. As such, miRNA that regulate TGF-beta signaling may hold promise as potential therapeutic targets. This review explores potential crosstalk between TGF-beta signaling and miRNA in AAA in order improve our understanding of this pathology and explore development of potential therapeutic targets.
作者：
Xiang, Qiong;Liu, Wen Feng;Zeng, Jing Lin;Deng, Yi Ming;Peng, Juan;...
期刊：
CURRENT MEDICINAL CHEMISTRY,2021年28(36):7446-7460 ISSN：0929-8673
通讯作者：
Liu, Lu Shan;Tang, Zhi Han
作者机构：
[Tang, Zhi Han; Liu, LS; Tang, ZH; Ren, Zhong; Liu, Lu Shan; Xiang, Qiong; Liu, Hui Ting; Zeng, Jing Lin; Deng, Yi Ming; Peng, Juan; Liu, Wen Feng; Jiang, Zhi Sheng] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hengyang Med Co, Hunan Inter Natl Sci & Technol Cooperat Base Arte, Hengyang City 421001, Hunan, Peoples R China.
通讯机构：
[Liu, LS; Tang, ZH] U;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hengyang Med Co, Hunan Inter Natl Sci & Technol Cooperat Base Arte, Hengyang City 421001, Hunan, Peoples R China.
摘要：
Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the “pleiotropic” effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.
作者机构：
Department of Cardiology, Guangdong Cardiovascu-lar institute, Provincial Key Laboratory of Coronary Heart Dis-ease Prevention, Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China;Institute of Cardiovascular Dis-ease and Key Laboratory for Arteriosclerology of Hunan Prov-ince, Hengyang Medical School, University of South China,Hengyang 421000, Hunan, China;[黄文晖; 丁兆慧; 黄澄] 广东省人民医院;[姜志胜] 华南大学
摘要：
Background Aortic dissection（AD） is a lethal medical emergency, which lacks specific biomarkers and effective pharmaceutical therapies. Increasing evidences have shown beneficial effect of angiotensin receptor blocker（ARB） drugs on downregulating transforming growth factor-β（TGF-β） pathway in Marfanoid AD. However,for non-Marfanoid AD, the effectiveness of ARB drugs, as well as the possible mechanisms, remains unclear.Methods Sprague Dawley（SD） rats were fed by gavage（i.g.） with either 150 mg/（kg·d） Hydroxyethyl diamine（AEEA） or isovolumic saline（normal saline group）. AEEA-induced SD rats were further randomly divided into three groups, including the AEEA+Losartan group [AEEA induction+20 mg/（kg·d） i.g. Losartan], the AEEA+Amlodipine group [AEEA induction + 6.5 mg/（kg · d） i.g. Amlodipine] and the AEEA + normal saline group（AEEA induction+isovolumic saline i.g.） group. Thus there were 4 groups with 12 mice in each. Tail blood pressure, aortic diameter and the number of aortic dissected lesions were measured in the above 4 groups 4 weeks thereafter. Western-blot was used to detect the expression of components of TGF-β/SMADs pathway, such as TGF-β1, drosophila mothers against decapentaplegic protein 2（Smad2）, Smad3, Smad4, protein kinase B（AKT）and phosphorylated AKT（p-AKT）. Results No significant difference of blood pressure was seen between the AEEA+Losartan group and the AEEA+Amlodipine group（P=0.81）. Ultrasound data indicated a significant reduction in aortic dilation of ascending aorta, aortic arch and descending aorta in Losartan intervention group relative to the Amlodipine intervention group（P<0.001）. Hematoxylin-eosin（HE） staining of aortic tissue demonstrated that under the setting of AEEA induction, AEEA+Losartan group had a lower incidence of aortic dissection than the AEEA+normal saline group and the AEEA+Amlodipine group（all P<0.01）. Losartan significantly reduced the expression of TGF-β1, Smad2, Smad3, Smad4 in aortic tissues of AEEA-induced rats（all P<0.05）. Conclusions Independent of BP reduction, Losartan, as an ARB drug, can prevent aortic dissection by inhibiting TGF-β/SMADs signaling pathway.[S Chin J Cardiol 2020;21（4）:269-276]
