Paras Kumar Mishra, PhD
Associate Professor at University of Nebraska Medical Center
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Paras Kumar Mishra, PhD
Associate Professor at University of Nebraska Medical Center
Diabetic Cardiomyopathy Research
Diabetes affects over 422 million people worldwide, significantly increasing the risk of heart failure—a condition where the heart is unable to pump sufficiently to meet the body's needs. Studies have shown that diabetes doubles the risk of developing heart failure, underscoring a pressing need for targeted research and therapeutic strategies. Despite advances in diabetes care, the specific mechanisms through which diabetes contributes to heart failure remain poorly understood, particularly the transition from metabolic disorder to cardiac dysfunction.
Diabetes-induced heart failure is distinct from non-diabetic heart failure due to increased myocardial lipotoxicity and a disproportionally higher risk in women compared to men. This underscores a critical need for specific research into the unique pathophysiological features of heart failure in diabetic patients. Our laboratory is dedicated to deciphering the complex molecular mechanisms underlying diabetic cardiomyopathy, aiming to develop novel therapeutics that can effectively address these challenges.
Our research primarily focuses on investigating the regulation of metabolic remodeling, cell death, and mitochondrial dysfunction within the diabetic heart. We are exploring innovative therapeutic avenues including miRNA mimics, hydrogen sulfide donors, and inhibitors of matrix metalloproteinase-9 (MMP9), each targeted at key aspects of the disease pathway.
Cardiomyocytes, the heart's muscle cells, rely heavily on mitochondria for energy production. In diabetic hearts, impaired glucose metabolism shifts the energy substrate preference from glucose to fatty acids, which are less efficient and increase mitochondrial stress. This stress leads to mitochondrial damage and dysfunction, which exacerbates the production of reactive oxygen species (ROS), further contributing to oxidative stress and cellular damage. Impaired mitophagy in diabetic hearts leads to the accumulation of damaged mitochondria, worsening the situation by promoting cell death and adverse cardiac remodeling. This cascade of events highlights the need for targeted research to prevent myocardial cell death and improve heart function in diabetic patients, ultimately aiming to mitigate the progression of diabetic cardiomyopathy and heart failure.
Diabetes-induced heart failure is distinct from non-diabetic heart failure due to increased myocardial lipotoxicity and a disproportionally higher risk in women compared to men. This underscores a critical need for specific research into the unique pathophysiological features of heart failure in diabetic patients. Our laboratory is dedicated to deciphering the complex molecular mechanisms underlying diabetic cardiomyopathy, aiming to develop novel therapeutics that can effectively address these challenges.
Our research primarily focuses on investigating the regulation of metabolic remodeling, cell death, and mitochondrial dysfunction within the diabetic heart. We are exploring innovative therapeutic avenues including miRNA mimics, hydrogen sulfide donors, and inhibitors of matrix metalloproteinase-9 (MMP9), each targeted at key aspects of the disease pathway.
Cardiomyocytes, the heart's muscle cells, rely heavily on mitochondria for energy production. In diabetic hearts, impaired glucose metabolism shifts the energy substrate preference from glucose to fatty acids, which are less efficient and increase mitochondrial stress. This stress leads to mitochondrial damage and dysfunction, which exacerbates the production of reactive oxygen species (ROS), further contributing to oxidative stress and cellular damage. Impaired mitophagy in diabetic hearts leads to the accumulation of damaged mitochondria, worsening the situation by promoting cell death and adverse cardiac remodeling. This cascade of events highlights the need for targeted research to prevent myocardial cell death and improve heart function in diabetic patients, ultimately aiming to mitigate the progression of diabetic cardiomyopathy and heart failure.
Mentoring is a cornerstone of my academic mission. My graduate students have achieved significant recognition, securing several prestigious national awards. Notably, one student won 1st place in The Science Coalition’s Fund It Forward Student Video Challenge in 2019 (Video Link) , while another garnered 2nd place at Research!America’s 2020 Flash Talks Competition during the National Health Research Forum (Link: https://www.unmc.edu/news.cfm?match=26235). Additionally, my students have been awarded the NIH F31, AHA Predoctoral, AHA Postdoctoral, and UNMC Presidential Graduate Fellowships and the UNMC Program of Excellence Assistantship, underscoring the high caliber of our research training and mentorship.
