Abstract
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.
| Original language | English |
|---|---|
| Article number | 817 |
| Number of pages | 13 |
| Journal | Frontiers in Physiology |
| Volume | 9 |
| Issue number | JUL |
| DOIs | |
| Publication status | Published - 9 Jul 2018 |
Keywords
- Aging
- Fibrosis
- Heart failure
- MicroRNAs
- MiRNAs
- MiRs
- Pathways
- Transcriptome
Cite this
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Age-related differential structural and transcriptomic responses in the hypertensive heart. / Marques, Francine Z.; Chu, Po Yin; Ziemann, Mark; Kaspi, Antony; Kiriazis, Helen; Du, Xiao Jun; El-Osta, Assam; Kaye, David M.
In: Frontiers in Physiology, Vol. 9, No. JUL, 817, 09.07.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Age-related differential structural and transcriptomic responses in the hypertensive heart
AU - Marques, Francine Z.
AU - Chu, Po Yin
AU - Ziemann, Mark
AU - Kaspi, Antony
AU - Kiriazis, Helen
AU - Du, Xiao Jun
AU - El-Osta, Assam
AU - Kaye, David M.
PY - 2018/7/9
Y1 - 2018/7/9
N2 - 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.
AB - 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.
KW - Aging
KW - Fibrosis
KW - Heart failure
KW - MicroRNAs
KW - MiRNAs
KW - MiRs
KW - Pathways
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85049867501&partnerID=8YFLogxK
U2 - 10.3389/fphys.2018.00817
DO - 10.3389/fphys.2018.00817
M3 - Article
VL - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
IS - JUL
M1 - 817
ER -