Broad-acting therapeutic effects of miR-29b-chitosan on hypertension and diabetic complications.

Autor:	Jensen DM; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Han P; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China., Mangala LS; Department of Gynecologic Oncology and Reproductive Medicine, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, UT MD Anderson Cancer Center, Houston, TX 77030, USA., Lopez-Berestein G; Center for RNA Interference and Non-Coding RNA, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX 77030, USA., Sood AK; Department of Gynecologic Oncology and Reproductive Medicine, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, UT MD Anderson Cancer Center, Houston, TX 77030, USA., Liu J; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Kriegel AJ; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Usa K; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Widlansky ME; Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Liang M; Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: mliang@mcw.edu.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2022 Nov 02; Vol. 30 (11), pp. 3462-3476. Date of Electronic Publication: 2022 Aug 13.
DOI:	10.1016/j.ymthe.2022.08.007
Abstrakt:	MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to test whether miR-29 could be developed as an effective, broad-acting, and safe therapeutic. Substantial accumulation of miR-29b and effective knockdown of Lypla1 in several mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH-NP) injected systemically at 200 μg/kg body weight. miR-29b-CH-NP, injected once every 3 days, significantly attenuated angiotensin II-induced hypertension. In db/db mice, miR-29b-CH-NP treatment for 12 weeks decreased cardiac and renal fibrosis and urinary albuminuria. In uninephrectomized db/db mice, miR-29b-CH-NP treatment for 20 weeks significantly improved myocardial performance index and attenuated proteinuria. miR-29b-CH-NP did not worsen abdominal aortic aneurysm in ApoE knockout mice treated with angiotensin II. miR-29b-CH-NP caused aortic root fibrotic cap thinning in ApoE knockout mice fed a high-cholesterol and high-fat diet but did not worsen the necrotic zone or mortality. In conclusion, systemic delivery of low-dose miR-29b-CH-NP is an effective therapeutic for several forms of cardiovascular and renal disease in mice. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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