Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation.
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.



We questioned whether allogeneic rat CDCs might be able to decrease manifestations of HFpEF in hypertensive rats.



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.



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.



CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.
Cedars-Sinai Heart Institute, Los Angeles, CA.
Romain
R
Gallet
Cedars-Sinai Heart Institute, Los Angeles, CA.
Geoffrey
G
de Couto
Cedars-Sinai Heart Institute, Los Angeles, CA.
Eli
E
Simsolo
Cedars-Sinai Heart Institute, Los Angeles, CA.
Jackelyn
J
Valle
Cedars-Sinai Heart Institute, Los Angeles, CA.
Baiming
B
Sun
Cedars-Sinai Heart Institute, Los Angeles, CA.
Weixin
W
Liu
Cedars-Sinai Heart Institute, Los Angeles, CA.
Eleni
E
Tseliou
Medical University of South Carolina and the RHJ Department of Veterans Affairs Medical Center, Charleston, SC.
Michael R
MR
Zile
Cedars-Sinai Heart Institute, Los Angeles, CA.
Eduardo
E
Marbán
Animal models; Cell therapy; Heart failure with preserved ejection fraction; diastolic function