Microtubule network remodeling in females with hypertension and early stage HFpEF

Microtubule densification has been tied to mechanical dysfunction in multiple types of heart failure. Current research fails to demonstrate the pathophysiology of microtubule remodeling in the early stages of heart failure. To better understand the physiological changes associated with diastolic dysfunction, the remodeling of the cardiac microtubule network during the early progression of hypertrophy and HFpEF must be studied. Comparing the degree of microtubule network remodeling, modifying enzyme levels, and microtubule associated protein changes between sexes under the same cardiometabolic and hemodynamics stress may provide insight into why women are twice as likely to have HFpEF than men. We assessed this with immunofluorescence staining and transcriptomic analysis of the tubulin code. Preliminary data suggests an increase in total microtubule network coverage and post translationalmodification in male and female obese rats compared to their lean controls. Studying changes in the microtubule network and microtubule associated protein concentrations in a rat model of HFpEF will allow us to identify and test targets for early intervention in diastolic heart disease. Future work will focus on understanding how modifications in the tubulin code in HFpEF impact force generation and work production of the myocardium and may be able to reverse diastolic dysfunction.