Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK-Reference-Cited by-同舟云学术

Metformin protects against pulmonary hypertension-induced right ventricular dysfunction in an age- and sex-specific manner independent of cardiac AMPK

Published:2023-08-01 Issue:2 Volume:325 Page:H278-H292
ISSN:0363-6135
Container-title:American Journal of Physiology-Heart and Circulatory Physiology
language:en
Short-container-title:American Journal of Physiology-Heart and Circulatory Physiology

Author:

McNair Benjamin D.¹,Polson Sydney M.¹,Shorthill Samantha K.¹,Yusifov Aykhan¹,Walker Lori A.²^ORCID,Weiser-Evans Mary C. M.³⁴^ORCID,Kovacs Elizabeth J.⁵⁶⁷^ORCID,Bruns Danielle R.¹⁸^ORCID

Affiliation:

1. Division of Kinesiology and Health, University of Wyoming, Laramie, Wyoming, United States

2. Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

3. Division of Renal Diseases and Hypertension, Department of Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

4. Consortium for Fibrosis Research and Translation, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

5. Division of GI, Trauma, and Endocrine Surgery, Department of Surgery, University of Colorado Denver, Aurora, Colorado, United States

6. Burn Research Program, University of Colorado Denver, Aurora, Colorado, United States

7. GI and Liver Innate Immune Program, University of Colorado Denver, Aurora, Colorado, United States

8. Wyoming WWAMI Medical Education Program, Laramie, Wyoming, United States

Abstract

Right ventricular (RV) function predicts survival in age-related disease, yet mechanisms of RV failure are unclear. We show that aged mice undergo exacerbated RV remodeling compared with young. We tested the AMPK activator metformin to improve RV function and show that metformin attenuates RV remodeling only in adult male mice via a mechanism that does not require cardiac AMPK. Metformin is therapeutic for RV dysfunction in an age- and sex-specific manner independent of cardiac AMPK.

Funder

American Heart Association

HHS | NIH | National Institute of General Medical Sciences

HHS | NIH | National Institute on Aging

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpheart.00124.2023

Reference42 articles.

1. Pulmonary arterial hypertension

2. Progressive Right Ventricular Dysfunction in Patients With Pulmonary Arterial Hypertension Responding to Therapy

3. Nationwide trends in inpatient admissions of pulmonary hypertension in the United States from 2000 to 2013

4. Age-Associated Increases in Pulmonary Artery Systolic Pressure in the General Population