Cerebral microvascular dysfunction in a rat model of heart failure with preserved ejection fraction

The aim of this research was to gain more insight into the pathophysiological mechanisms underlying cerebral microvascular dysfunction in a rat model of heart failure with preserved ejection fraction (HFpEF). This thesis investigated the cognitive and cardiovascular phenotype of a rat model of comorbidities (obesity, diabetes, hypertension, HFpEF). Cerebral microvascular dysfunction was assessed by cerebral blood flow measurements, quantification of blood brain barrier leakages, and 3D quantification of the cerebral and cardiac vascular network. Through transcriptomic analysis, KLF2 and TRPV4 were identified as important targets in microvascular dysfunction in cerebral small vessel disease. This thesis contributes to a better understanding of cerebral microvascular dysfunction in a HFpEF model, and highlights the potential of a multi-action, biomechanical approach that could have therapeutic benefits for various organs.