Abstract | BACKGROUND: The pathogenesis of HFpEF is unclear, but fibrosis, inflammation and hypertrophy have been put forth as likely contributors. CDCs are heart-derived cell products with anti-fibrotic and anti-inflammatory properties. OBJECTIVES: We questioned whether allogeneic rat CDCs might be able to decrease manifestations of HFpEF in hypertensive rats. METHODS: Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high- salt diet for 6-7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. RESULTS: High- salt rats developed hypertension, left ventricular (LV) hypertrophy and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed major HFpEF-related, CDC-reversed changes in numerous transcripts, including many involved in inflammation and/or fibrosis. CONCLUSION:
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Authors | Romain Gallet, Geoffrey de Couto, Eli Simsolo, Jackelyn Valle, Baiming Sun, Weixin Liu, Eleni Tseliou, Michael R Zile, Eduardo Marbán |
Journal | JACC. Basic to translational science
(JACC Basic Transl Sci)
2016 Jan-Feb
Vol. 1
Issue 1-2
Pg. 14-28
ISSN: 2452-302X [Print] United States |
PMID | 27104217
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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