journal article·2024-10Open access

miR‐30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil

Xuchun Liang, Jingwen Zhou, Hongyun Wang, Ziyi Zhang, Mingming Yin, Yujiao Zhu, Lin Li, Chen Chen, Meng Wei, Meiyu Hu, Cuimei Zhao, Jianhua Yao, Guoping Li, Anh‐Tuan Dinh‐Xuan, Junjie Xiao, Yihua Bei

Advanced Science· Volume 11· Issue 40

Abstract

Abstract Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular smooth muscle cell (PASMC) function and vascular remodeling. MiR‐30d plays an important role in the pathogenesis of several cardiovascular disorders. However, the function of miR‐30d in PAH progression remained unknown. Our study shows that circulating miR‐30d level is significantly reduced in the plasma from PAH patients. In miR‐30d transgenic (TG) rats, overexpressing miR‐30d attenuates monocrotaline (MCT)‐induced pulmonary hypertension (PH) and pulmonary vascular remodeling. Increasing miR‐30d also inhibits platelet‐derived growth factor‐bb (PDGF‐bb)‐induced proliferation and migration of human PASMC. Metadherin (MTDH) and phosphodiesterase 5A (PDE5A) are identified as direct target genes of miR‐30d. Meanwhile, nuclear respiratory factor 1 (NRF1) acts as a positive upstream regulator of miR‐30d. Using miR‐30d knockout (KO) rats treated with sildenafil, a PDE5A inhibitor that is used in clinical PAH therapies, it is further found that suppressing miR‐30d partially attenuates the beneficial effect of sildenafil against MCT‐induced PH and vascular remodeling. The present study shows a protective effect of miR‐30d against PAH and pulmonary vascular remodeling through targeting MTDH and PDE5A and reveals that miR‐30d modulates the beneficial effect of sildenafil in treating PAH. MiR‐30d should be a prospective target to treat PAH and pulmonary vascular remodeling.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Pulmonary Hypertension Research and Treatments · Renin-Angiotensin System Studies · MXene and MAX Phase Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) and School of Life Science Shanghai University Nantong 226011 China

Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education) Shanghai University Shanghai 200444 China

Cardiac Regeneration and Ageing Lab Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair School of Medicine Shanghai University Shanghai 200444 China

Department of Cardiology Shanghai Tongji Hospital Tongji University School of Medicine Shanghai 200065 China

Department of Cardiology Tenth People's Hospital School of Medicine Tongji University Shanghai 200090 China

Department of Cardiology Shigatse People's Hospital Tibet 857000 China

Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA

Lung Function & Respiratory Physiology Units Department of Respiratory Physiology and Sleep Medicine Cochin & George Pompidou Hospitals Assistance Publique‐Hôpitaux de Paris (APHP) Centre University Paris Cité Paris 75014 France

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shanghai Municipality · Natural Science Foundation of Tibet Autonomous Region

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