Early Changes in Cardiac Macrophage Subsets in Heart Failure with Preserved Ejection Fraction

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dc.catalogadorjlo
dc.contributor.authorGutiérrez Cisternas, Danae Abigail
dc.contributor.authorCordero Fernández, Karina Alejandra
dc.contributor.authorSepúlveda Sarmiento, Ruth Angélica
dc.contributor.authorVenegas, Camilo
dc.contributor.authorAltamirano, Diego
dc.contributor.authorCandia, Camila
dc.contributor.authorRamírez Rojas, Gigliola
dc.contributor.authorAraos, Patricio
dc.contributor.authorAmador, Cristian A.
dc.contributor.authorHermoso, Marcela A.
dc.contributor.authorGabrielli Nervi, Luigi Arnaldo
dc.contributor.authorJalil Milad, Jorge Emilio
dc.contributor.authorOcaranza Jeraldino, María Paz
dc.date.accessioned2025-10-30T19:00:51Z
dc.date.available2025-10-30T19:00:51Z
dc.date.issued2025
dc.description.abstractHeart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by left ventricular diastolic dysfunction, exercise intolerance, low-grade chronic inflammation, and comorbidities such as hypertension, obesity, and glucose intolerance. Myocardial infiltration by activated macrophages has been proposed as a mechanism linking low-grade inflammation to increased diastolic LV stiffness in HFpEF. Changes in the relative abundance of cardiac macrophage populations may precede and promote the development of HFpEF in the aged heart. This study aimed to characterize the cardiac macrophage subsets that predominate during progression from experimental preclinical to established HFpEF. To generate the model, wild-type male C57BL/6N mice were randomized to control chow or a combination of high-fat diet plus L-NAME in drinking water for 5 weeks (asymptomatic pre-HFpEF) or 15 weeks (established HFpEF). At the end of each period, we measured body weight, running distance, metabolic biomarkers, systolic and diastolic blood pressure, myocardial function and morphology, cardiac remodeling by hypertrophic markers, morphometric analyses, fibrosis, cytokines TNF-α and IL-10, cardiac macrophage phenotype profiles (CCR2+ and CCR2−), and AMP-Activated Protein Kinase (AMPK)activity.Significant changes in myocardial macrophage populations were observed at 5 weeks (pre-HFpEF), specifically a decrease in resident reparative CCR2−MHCII− and increase in proinflammatory CCR2+MHCII+ macrophages. These early changes were associated with higher circulating TNF-α, decreased myocardial AMPK activation, and more severe myocardial fibrosis. At 15 weeks (established HFpEF), proinflammatory CCR2+MHCII+ macrophage levels remained elevated in the myocardium; whereas the initial number of resident reparative CCR2−MHCII- levels was reduced, it subsequently returned to baseline. In this model of HFpEF induced by a high-fat diet and L-NAME, which produced obesity, glucose intolerance, and hypertension, myocardial resident reparative CCR2−MHCII− macrophages decreased and proinflammatory CCR2+MHCII+ macrophages increased during preclinical stages. These early changes in cardiac macrophage profile were associated with low-grade inflammation and myocardial remodeling and preceded the onset of HFpEF.
dc.fechaingreso.objetodigital2025-10-30
dc.format.extent19 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/ijms262010196
dc.identifier.urihttps://doi.org/10.3390/ijms262010196
dc.identifier.urihttps://www.mdpi.com/1422-0067/26/20/10196
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/106442
dc.information.autorucNo Informado; Gutiérrez Cisternas, Danae Abigail; S/I; 1357065
dc.information.autorucNo Informado; Cordero Fernández, Karina Alejandra; S/I; 1367833
dc.information.autorucS/I; Sepúlveda Sarmiento, Ruth Angélica; S/I; 1267503
dc.information.autorucS/I; Ramírez Rojas, Gigliola; S/I; 1001936
dc.information.autorucEscuela de Medicina; Gabrielli Nervi, Luigi Arnaldo; 0000-0002-1551-7147; 11086
dc.information.autorucEscuela de Medicina; Jalil Milad, Jorge Emilio; 0000-0001-6877-2072; 99946
dc.information.autorucEscuela de Medicina; Ocaranza Jeraldino, María Paz; 0000-0002-4915-6378; 1001254
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaInternational Journal of Molecular Sciences
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHeart failure
dc.subjectDiabetes
dc.subjectHypertension
dc.subjectCardiometabolic syndrome
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleEarly Changes in Cardiac Macrophage Subsets in Heart Failure with Preserved Ejection Fraction
dc.typeartículo
sipa.codpersvinculados1357065
sipa.codpersvinculados1367833
sipa.codpersvinculados1267503
sipa.codpersvinculados1001936
sipa.codpersvinculados11086
sipa.codpersvinculados99946
sipa.codpersvinculados1001254
sipa.trazabilidadORCID;2025-10-27
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