Abstract 17241: The Bone Marrow-Mediated Adipokine Resistin Like Alpha Impairs Cardiac Recovery Through Apoptosis and Fibrosis After Myocardial Infarction

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Abstract

Introduction: Resistin like alpha (Retnla) is characterized as an adipokine and known to modulate cholesterol homeostasis, and the involvement of Fizz1 in cardiac pathology is unknown.

Hypothesis: Retnla would be involved in the progress of cardiac pathology.

Methods: Methods: Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and tissues were collected for further analyses. Bone marrow cells were isolated from KO mice or TG mice to transplant to the WT infarcted heart. To study the effect of Retnla, cardiomyocytes or cardiac fibroblasts were treated with recombinant protein Retnla.

Results: Cardiac function was significantly preserved in the KO group, while worsen in the TG group. Importantly, angiogenesis was substantially increased in the KO group, while significantly decreased in the TG group. Microfill staining and aortic ring assay also showed better angiogenetic events in the KO group. We found the number of bone marrow cells was notably higher in the KO mice, while lower in the TG mice compared with WT mice. To examine the effect of bone marrow cells on the infarcted heart, we injected bone marrow cells from KO or TG mice to recipient WT mice. Two weeks after MI, recipient WT mice transplanted with bone marrow cells from KO mice showed better angiogenesis and reserved cardiac function after MI. On the other hand, angiogenesis and cardiac function were reduced in the WT mice transplanted with bone marrow cells from TG mice. Next, we assessed the cell death and signaling molecules, and MI-induced cardiac apoptosis was markedly suppressed in the KO group. Anti-apoptotic bcl2 was decreased, while stress-induced p38 and cell cycle arrest inducer p21 were significantly increased in Retnla-treated cardiomyocytes. Conversely, Retnla -treated cardiac fibroblasts showed a strikingly suppression of p21. Our data showed better cardiac recovery in the Retnla KO group than in the TG group.

Conclusions: Enhanced angiogenesis and reduced apoptosis in Retnla KO mice are associated with substantial cardiac recovery. We suggested that bone marrow cells may largely contribute to the progress of cardiac pathology.

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