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  3. Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model

Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model

  • Respir Res. 2023 Aug 17;24(1):202. doi: 10.1186/s12931-023-02501-7.
Meidan Kuang 1,  Yilin Chen 1,  Yue Xing 1,  Min Du 1,  Huazhuo Feng 1,  Qifeng Yang 1,  Dongmei Wen 1,  Xuanyi Li 1,  Kai Yang 1,  Ziying Lin 1,  Ning Lai 1,  Qian Jiang 1,  Shiyun Liu 1,  Dansha Zhou 1,  Wei Hong 1,  Xin Fu 1,  Wenju Lu 1,  Tengteng Zhao 2,  Jian Wang 3 4,  Yuqin Chen 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, GMU-GIBH Joint School of Life Sciences, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
  • 2 The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.
  • 3 State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, GMU-GIBH Joint School of Life Sciences, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. jiw037@health.ucsd.edu.
  • 4 Guangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, 510320, Guangdong, China. jiw037@health.ucsd.edu.
  • 5 State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, GMU-GIBH Joint School of Life Sciences, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. yqchen@gzhmu.edu.cn.
PMID: 37592245 DOI: 10.1186/s12931-023-02501-7
Abstract

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and Other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

Keywords

Echocardiography; Pulmonary hypertension; Rats; Right heart failure.

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