UAB Department of Biomedical Engineering chair Jianyi “Jay” Zhang, M.D., Ph.D., was recently awarded a new R01 grant from the National Heart, Lung, and Blood Institute for the proposal, “Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodeling.” The grant totals $2.1 million for the project period that began in July 2021 and runs through June 2025.  

zhang2021 245Patients with severe acute myocardial infarction (AMI) often progress to end-stage congestive heart failure (CHF), which is one of the most significant problems facing public health today. The molecular and cellular basis for progressive heart failure is the result of the inability of damaged and apoptic myocytes to be replaced. The central objective of this proposal is to “turn back the clock” of the myocyte cell cycle for myocardial regeneration.

Previous research observations of Zhang’s lab suggest that mammalian cardiomyocytes can be induced to re-enter the cell cycle by changes in the activity of cell-cycle regulatory molecules. This strategy may overcome both the limited regenerative potential of endogenous cardiomyocytes and the exceptionally poor rate of engraftment associated with transplanted cells or engineered tissues.

“Our specific aims,” Zhang says, “are to identify the key regulators that promote cell-cycle activity in the hearts of early neonatal pigs after myocardial injury, to engineer bioengineered cardiac muscle patches (hCMPs) of previously unattainable sizes and thicknesses that are functionally mature and primed for in-vivo vascularization, and to evaluate the effectiveness of the hCMP constructs for myocardial recovery and remuscularization in a large swine animal model of myocardial injury with optical mapping techniques.”

The project’s main goal is to remuscularize the injured left ventricle of the heart from within by identifying and manipulating factors that regulate the cardiomyocyte cell cycle, and from outside by engineering hCMPs containing cardiomyocytes that are capable of proliferating after transplantation. The researchers will use state-of-the-art molecular biology and imaging to demonstrate these results.

Collaborators on this study include co-investigators in the UAB Department of Biomedical Engineering, Jack Rogers, Ph.D., Professor, and Yuji Nakada, M.D., Ph.D., Associate Professor.

“This study,” Zhang says, “will allow us to gain a deeper understanding of congestive heart failure and, in turn, will have major implications in developing its treatment and cure.”

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