2026-06-14T23:37:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/274072026-04-10T00:21:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Villalba-Orero, María author López-Olañeta, Marina author Campos-Olmo, Belén author Jimenez-Carretero, Daniel author Sánchez, Lucía author Sánchez-Cabo, Fátima author Ausiello, Antonella author Cañas-Álvaro, Rodrigo author Camafeita, Emilio author Vázquez, Jesús author García-Pavía, Pablo author Pascual-Figal, Domingo author Lara-Pezzi, Enrique author 2025-01 Heart failure with preserved ejection fraction (HFpEF) is a major public health problem characterized by multiple simultaneous comorbidities whose specific contribution is challenging to disentangle in humans, leading to a generalized therapeutic approach that may not account for the underlying pathology. We followed distinct mouse models of major HFpEF comorbidities for 2.5 years to unveil their specific contribution to the syndrome. All comorbidities contributed to HFpEF through partially distinct routes. Aging alone resulted in HFpEF in old age, with delayed left ventricular relaxation and kidney fibrosis. Obesity induced a faster deterioration of relaxation associated with enlarged left ventricle and liver fibrosis. Hypertension caused delayed ventricular relaxation independent from structural changes that preceded left atrial dilatation linked to aortic stiffness and increased fibrosis in myocardium and kidney. Chronic intermittent hypoxia led to HFpEF and relaxation impairment associated with pulmonary hypertension. Hyperglycemia accelerated diastolic dysfunction and HFpEF onset associated with reduced arterial flow and left ventricular remodeling. Therefore, the pathological substrates contributing to HFpEF included cardiac and noncardiac alterations with differential features for each comorbidity. Critically, the characteristics linked to diastolic dysfunction and HFpEF across the various comorbidities agreed with phenogroups observed in human patients. The identification of time-dependent pathological features provides a comprehensive picture of HFpEF progression associated with each comorbidity. Circ Heart Fail. 2025 Jan;18(1):e011724. CIRCULATION-HEART FAILURE 39611257 https://hdl.handle.net/20.500.12105/27407 aging heart failure, diastolic hyperglycemia hypertension obesity Unraveling Comorbidities Contribution to Cardiac Diastolic Dysfunction and Heart Failure.