2026-06-14T23:36:52Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/274072026-04-10T00:21:26Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
2026-04-09T11:11:51Z
2026-04-09T11:11:51Z
2025-01
Circ Heart Fail. 2025 Jan;18(1):e011724.
CIRCULATION-HEART FAILURE
39611257
https://hdl.handle.net/20.500.12105/27407
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.
eng
aging
heart failure, diastolic
hyperglycemia
hypertension
obesity
Unraveling Comorbidities Contribution to Cardiac Diastolic Dysfunction and Heart Failure.
research article
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11d82f1f8b3162561449476090923f20
1601302
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Unravelling comorbidities contribution to cardiac_Circ Heart Fail_2025.pdf