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Immunomodulation Therapy for Cardiac Regeneration in a Rat Model of Diabetic Cardiomyopathy and Myocardial Infarction

Aggarwal, Arun
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1684770321732047

Abstract Details

2023, MS, University of Cincinnati, Engineering and Applied Science: Biomedical Engineering.
Diabetes mellitus is widely acknowledged as one of the most prevalent metabolic diseases, affecting millions of people around the world. In addition to presenting the generally observed metabolic deficiencies, diabetes can also severely impact other body systems by impairing circulation, promoting neuropathy, and stalling the wound healing process. In particular, the cardiovascular system is often affected by diabetic co-pathologies; these can result from both increased inflammation and actual changes in the structure of cardiac tissue. One such cardiac co-pathology is diabetic cardiomyopathy, or DCM. DCM presents primarily as impaired contraction of cardiac muscle in conjunction with progressive fibrosis, which is characterized by increased collagen deposition, increased cardiomyocyte apoptosis, and/or left ventricular hypertrophy. These observed effects are likely due to alterations within the diabetic microenvironment. Additionally, prior studies in the field of diabetic wound healing have shown that the hyperglycemic environment can alter the behavior of vascular cells, thus stalling the healing process in the chronic inflammatory phase. Since diabetic cardiomyopathy has been linked to increased occurrences of myocardial infarction and more severe post-infarct complications, there is a need for better therapeutic options than the currently employed treatment method, which relies solely on basic glycemic control. This study explores the use of a bioengineered RAD16-II (RARADADARARADADA) peptide nanofiber scaffold as a delivery vehicle for exogenous matrix metalloprotease 2 (MMP-2). This injectable scaffold/protein combination is suggested as a potential therapy for the severely fibrotic phenotype associated with diabetic cardiomyopathy since it has been shown that MMP-2 levels are reduced in diabetic cardiac tissue. Furthermore, MMP-2 primarily functions in maintaining the composition of the extracellular matrix by degrading fibrillar collagen; thus, decreased MMP-2 levels could be directly related to the observed fibrotic phenotype of DCM. Based on the data collected, nanofiber-based treatment provides a protective effect on cardiac functional parameters post-infarction under conditions of diabetic cardiomyopathy and Myocardial Infarction (MI) in a streptozotocin rodent model of type I diabetes. These observations are confirmed with immunohistochemistry results indicating that nanofiber treatment dramatically reduces formation of fibrous scarring after MI while also stimulating regenerative healing within the infarcted scar area. Interestingly, the presence of differentiated pro-regenerative macrophages at 8 weeks post-infarct confirms continuous and active remodeling beyond the initial inflammatory response. Overall, the peptide nanofiber scaffold provides a suitable delivery vehicle for slow, controlled release of MMP-2 and appears to promote long-term tissue regeneration even after severe ischemic injury in the diabetic heart.
Daria Narmoneva, Ph.D. (Committee Chair)
Stacey Schutte, Ph.D. (Committee Member)
T. Douglas Mast, Ph.D. (Committee Member)
44 p.
Biomedical Research
Diabetic Cardiomyopathy; Bioengineered Scaffold; Myocardial Infarction

Recommended Citations

Citations

  • Aggarwal, A. (2023). Immunomodulation Therapy for Cardiac Regeneration in a Rat Model of Diabetic Cardiomyopathy and Myocardial Infarction [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1684770321732047

    APA Style (7th edition)

  • Aggarwal, Arun. Immunomodulation Therapy for Cardiac Regeneration in a Rat Model of Diabetic Cardiomyopathy and Myocardial Infarction. 2023. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1684770321732047.

    MLA Style (8th edition)

  • Aggarwal, Arun. "Immunomodulation Therapy for Cardiac Regeneration in a Rat Model of Diabetic Cardiomyopathy and Myocardial Infarction." Master's thesis, University of Cincinnati, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1684770321732047

    Chicago Manual of Style (17th edition)

ucin1684770321732047
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This open access ETD is published by University of Cincinnati and OhioLINK.