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Age-related differential structural and transcriptomic responses in the hypertensive heart

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journal contribution
posted on 2018-07-09, 00:00 authored by F Z Marques, P Y Chu, Mark ZiemannMark Ziemann, A Kaspi, H Kiriazis, X J Du, A El-Osta, D M Kaye
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.

History

Journal

Frontiers in physiology

Volume

9

Article number

817

Pagination

1 - 13

Publisher

Frontiers

Location

Lausanne, Switzerland

eISSN

1664-042X

Language

eng

Publication classification

C Journal article; C1.1 Refereed article in a scholarly journal

Copyright notice

2018, Marques, Chu, Ziemann, Kaspi, Kiriazis, Du, El-Osta and Kaye.