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Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function

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  • معلومة اضافية
    • بيانات النشر:
      MDPI AG
    • الموضوع:
      2024
    • Collection:
      Directory of Open Access Journals: DOAJ Articles
    • نبذة مختصرة :
      Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.
    • ISSN:
      1422-0067
      1661-6596
    • Relation:
      https://www.mdpi.com/1422-0067/25/15/8054; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/a73b910647364264af294cd9257363c7
    • الرقم المعرف:
      10.3390/ijms25158054
    • الدخول الالكتروني :
      https://doi.org/10.3390/ijms25158054
      https://doaj.org/article/a73b910647364264af294cd9257363c7
    • الرقم المعرف:
      edsbas.4BE5C9EB