Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats. Physiol Genomics 2012 Oct 02;44(19):925-33
Date
08/02/2012Pubmed ID
22851760Pubmed Central ID
PMC3472462DOI
10.1152/physiolgenomics.00170.2011Scopus ID
2-s2.0-84867170169 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce fibrosis in rodents after myocardial infarction, resulting in an overall improvement in left ventricular function. Little is known about the effectiveness of BMMNC therapy in hypertensive heart disease. In the current study, we show that delivery of BMMNCs from hypertension protected SS-13(BN)/MCWi donor rats, but not BMMNC from hypertension susceptible SS/MCWi donor rats, resulted in 57.2 and 83.4% reductions in perivascular and interstitial fibrosis, respectively, as well as a 60% increase in capillary-to-myocyte count in the left ventricles (LV) of hypertensive SS/MCWi recipients. These histological changes were associated with improvements in LV compliance and relaxation (103 and 46.4% improvements, respectively). Furthermore, improved diastolic function in hypertensive SS/MCWi rats receiving SS-13(BN)/MCWi derived BMMNCs was associated with lower clinical indicators of heart failure, including reductions in end diastolic pressure (65%) and serum brain natriuretic peptide levels (49.9%) with no improvements observed in rats receiving SS/MCWi BMMNCs. SS/MCWi rats had a lower percentage of endothelial progenitor cells in their bone marrow relative to SS-13(BN)/MCWi rats. These results suggest that administration of BMMNCs can prevent or reverse pathological remodeling in hypertensive heart disease, which contributes to ameliorating diastolic dysfunction and associated symptomology. Furthermore, the health and hypertension susceptibility of the BMMNC donor are important factors influencing therapeutic efficacy, possibly via differences in the cellular composition of bone marrow.
Author List
Parker SJ, Didier DN, Karcher JR, Stodola TJ, Endres B, Greene ASMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Blood Pressure
Bone Marrow Transplantation
Coronary Vessels
Diastole
Echocardiography
Fibrosis
Heart Diseases
Immunohistochemistry
Leukocytes, Mononuclear
Male
Natriuretic Peptide, Brain
Polymerase Chain Reaction
Quantum Dots
Rats
Rats, Inbred Dahl
Ventricular Remodeling