Date of Award

2025-05-01

Degree Name

Doctor of Philosophy

Department

Environmental Science and Engineering

Advisor(s)

Ahemad El Gendy

Second Advisor

Binata Joddar

Abstract

Heart failure, an abnormal heartbeat, and sudden death are all possible outcomes of preexisting or underlying cardiac disease. Heart disease is highly correlated with diabetes, causing heart pain and shortness of breath. In patients without other cardiac conditions, diabetic cardiomyopathy is a process that affects the myocardium over a long period of time. This disease has a complicated pathophysiology that can be broken down into processes that lead to diastolic and/or systolic dysfunction. However, the pathophysiological differences between normal, diabetic, and diseased cardiac tissues have not been thoroughly studied. Therefore, in this research, we directed our efforts to perform a pilot characterization to distinguish between Type II diabetic and non-diabetic human ventricular myocardium structure and physiology. Two distinct human samples were used in the research: Tissue samples from adult ventricular myocardium from (1) diabetic and (2) nondiabetic donors. These samples were subjected to the following analysis, including (i) surface and micro-structural analysis; (ii) mechanical characterization; and (iii) gene expression studies. The surface and structural details of the tissues were examined with scanning electron microscopy (SEM) imaging. However, soft tissue analysis remains a challenge because of its limited contrast nature, which makes it difficult to distinguish structures in the soft tissue, such as the heart muscle. The primary techniques were pivotal to our study, there are some parallel methods adopted to strengthen our existing methods. HIM [Helium Ion Microscopy], Light sheet microscopy with Lectin 488 and propidium Iodide and fast green staining, and Micro CT with Lugol's agent. The mechanical properties of the tissue samples were studied by rheological analysis. Following (ribonucleic acid) RNA extraction, the samples were subjected to RNA sequencing to determine gene expression in both samples. The results of this fundamental study demonstrated that cardiac tissue structure and function could be clearly distinguished between diabetic and non-diabetic ventricular myocardium. Outcomes will drive the creation of an engineered diabetic human tissue on a chip model for drug studies and other mechanistic investigations.

Language

en

Provenance

Received from ProQuest

File Size

83 p.

File Format

application/pdf

Rights Holder

Haritha Keerthi

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