Energetics-transcription coupling in hypertensive heart

High blood pressure can lead to adverse changes in the hearts structure and function, a condition known as hypertensive cardiomyopathy. This is a growing issue worldwide, especially as populations age and there are no permanent cures available. Recent studies suggest that one of the first problems in heart cells caused by high blood pressure is an energy shortage. However, its still unclear how this energy deficiency leads to harmful changes in the cells genetic programs, which make the heart function poorly. In this project, we will study how stressed mitochondria (the energy producers in cells) might send signals to the cell`s control center (nucleus) in specific, spatially restricted areas near the nucleus. We will follow the hypothesis that these subcellular areas act as control hubs for energy production, cellular contractility, and gene activity in heart cells. Our goal is to create a detailed understanding of the signaling communication between the mitochondria and the cell nucleus, as well as how this communication determines the overall fate of heart cells. We will start by closely examining mitochondrial function and structure over time, especially around the nucleus. This will help us understand how changes in these energy producers affect the cell`s genetic activity early in the development of heart problems. Then, we will correlate mitochondrial fitness with the genetic activity in the cells to find the earliest and most treatable changes leading to the progression of the disease. We will also test if restoring mitochondrial quality and functionality can reverse the harmful genetic changes caused by high blood pressure. Finally, we will apply our findings to a group of patients with similar heart phenotypes to ensure our discoveries are relevant to clinical settings. We anticipate that this project will shed light on how heart cells get exhausted and how subsequent molecular processes develop into hypertensive cardiomyopathy. This understanding may lead to the design of new treatment strategies for patients at risk of developing hypertensive cardiomyopathy.