Age-Related Differential Structural and Transcriptomic Responses in the Hypertensive Heart

Frontiers in Physiology

Xiao-Jun Du¹  Assam El-Osta²  Francine Z. Marques³  Antony Kaspi⁴  Mark Ziemann⁴  Helen Kiriazis⁵  David M. Kaye⁶  Po-Yin Chu⁷ 

[1] Central Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia;Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia;Department of Pharmacology, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia;Epigenetics in Human Health and Disease, Department of Diabetes, Monash University, Melbourne, VIC, Australia;Experimental Cardiology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Heart Centre, Alfred Hospital, Melbourne, VIC, Australia;Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong;

关键词: heart failure;    aging;    fibrosis;    microRNAs;    miRNAs;    miRs;   

DOI  :  10.3389/fphys.2018.00817

来源: DOAJ

【 摘 要 】

While aging is a critical risk factor for heart failure, it remains uncertain whether the aging heart responds differentially to a hypertensive stimuli. Here we investigated phenotypic and transcriptomic differences between the young and aging heart using a mineralocorticoid-excess model of hypertension. Ten-week (“young”) and 36-week (“aging”) mice underwent a unilateral uninephrectomy with deoxycorticosterone acetate (DOCA) pellet implantation (n = 6–8/group) and were followed for 6 weeks. Cardiac structure and function, blood pressure (BP) and the cardiac transcriptome were subsequently examined. Young and aging DOCA mice had high BP, increased cardiac mass, cardiac hypertrophy, and fibrosis. Left ventricular end-diastolic pressure increased in aging DOCA-treated mice in contrast to young DOCA mice. Interstitial and perivascular fibrosis occurred in response to DOCA, but perivascular fibrosis was greater in aging mice. Transcriptomic analysis showed that young mice had features of higher oxidative stress, likely due to activation of the respiratory electron transport chain. In contrast, aging mice showed up-regulation of collagen formation in association with activation of innate immunity together with markers of inflammation including cytokine and platelet signaling. In comparison to younger mice, aging mice demonstrated different phenotypic and molecular responses to hypertensive stress. These findings have potential implications for the pathogenesis of age-related forms of cardiovascular disease, particularly heart failure.

【 授权许可】

Unknown