Periodic Reporting for period 5 - DIAMONDCOR (A molecular approach to treat diabetes mellitus onset dependent coronaropathy)
Reporting period: 2023-01-01 to 2023-12-31
As frequent and severe metabolic disorder, diabetes mellitus (DM) affected 537 million people worldwide in 2021 with rising incidence, especially in developed countries. In Europe, 68.9 million patients are estimated to suffer from DM in 2035 and nearly 10% of the population in 2045. As one of the most challenging consequences, diabetes inflicts cardiovascular disease leading to cardiomyopathy and cardiac death: Diabetes affects many organ systems including micro- and macro-circulation. As most frequent sequela, diabetes mellitus affects coronary vessel function and thus proper blood perfusion of the heart. Consistently, myocardial infarction and subsequent heart failure are the most common causes of death in diabetic patients.
Therefore the overall objective of DIAMONDCOR is to address micro-vessel disease in diabetic hearts. We aim to assess the reversibility of diabetic myocardial dysfunction by specific molecular interventions for vessel stabilization as well as neovascularization.
Therefore the overall objective of DIAMONDCOR is to address micro-vessel disease in diabetic hearts. We aim to assess the reversibility of diabetic myocardial dysfunction by specific molecular interventions for vessel stabilization as well as neovascularization.
Diabetes mellitus leads to an impairment of the cardiac microcirculation, thereby influencing cardiac function. Furthermore, theses changes in the diabetic heart lead to an increase in infarct size as well as a reduced cardiac function after acute myocardial infarcts in pigs. Monitoring of the microcirculatory state in diabetic cardiomyopathy is important and is one of the major goals in DIAMONDCOR. Furthermore, we have evidence, that normalization of the micro-circulation in diabetic cardiomyopathy leads to an improved cardiac function, thereby reducing signs of heart failure. The signature of the diabetic endothelium is in part comparable to other cardiovascular risk factors, such as aging and hypercholesterolemia, enabling for common preventive therapeutic strategies in cardiovascular risk factor patient. In addition to endothelial dysfunction, extracellular vesicles are increased in number and different in content in diabetes, thereby further contributing to the diabetic cardiomyopathy via cell-cell communication.
Within DIAMONDCOR we developed novel imaging modalities, which can be translated to the human situation and might be suitable for the monitoring of diabetic cardiomyopathy and other cardiovascular risk factor dependent cardiomyopathies. In addition these novel imaging modalities might improve monitoring of therapeutic success in cardiac disease. DIAMONDCOR enabled us to have deeper insight into the molecular and cellular changes in diabetes and to compare those to other models of cardiovascular risk factors which we have in our group. Molecular signature as well as cellular changes and even extracellular vesicles showed similar pattern upon diabetes, hypercholesterolemia and aging, enabling us to develop novel come therapeutic approaches for multiple cardiovascular risk factors and novel therapeutic approaches, such as gene editing.