Background: The plasticity of endothelial cells (ECs) is crucial for tissue response to injury. Myocardial infarction can profoundly affect EC function, leading to a shift toward mesenchymal differentiation.Methods: We utilized human single‐nucleus RNA sequencing data to investigate the dynamic changes and cellular interactions between normal and post‐infarction ECs.Results: We identified two distinct subpopulations of ECs: A transient subpopulation characterized by short‐term mesenchymal gene expression and a long‐term subpopulation characterized by myocardial gene expression. Trajectory analysis revealed the differentiation pathways and potential roles over time and space. Furthermore, we uncovered the proliferation, differentiation, hypoxic, and inflammatory responses of ECs to injury.Conclusions: Our study provides a comprehensive and detailed characterization of endothelial cell states, highlighting the role of activated endothelial cell subpopulations in promoting inflammation and tissue repair after infarction.

In 2023, the American Heart Association (AHA) introduced the Cardiovascular-Kidney-Metabolic (CKM) syndrome concept to address the substantial burden of interrelated cardiovascular, kidney, and metabolic disorders. The framework highlights that chronic kidney disease (CKD) significantly accelerates CKM syndrome progression and increases cardiovascular risk, an effect that may be closely paralleled by aldosterone excess. Excess aldosterone can arise from renin-dependent aldosteronism (RDA), a primarily physiological state (not discussed in this review), or from renin-independent aldosteronism (RIA). RIA is a pathophysiologically relevant condition characterized by persistent autonomous activation, bypassing normal renin-angiotensin-aldosterone system (RAAS) regulation. Its most recognized form is PA, a prevalent, multidimensional disorder spanning a continuum from subclinical to overt autonomous aldosterone production. This leads to inappropriately elevated aldosterone relative to suppressed renin and sodium levels. PA is a leading cause of secondary hypertension and elevates the risk of metabolic and cardiorenal disorders, showing substantial overlap with CKM syndrome. Despite its clinical significance, the specific relationship between PA and CKM syndrome remains insufficiently investigated. This review synthesizes evidence from three key perspectives: (1) Epidemiology and clinical data show that PA spans a spectrum from subclinical to overt stages and is strongly associated with driving and accelerating the progression of CKM syndrome; (2) Therapeutically, targeted treatment of PA mitigates the adverse effects of aldosterone on CKM syndrome progression; and (3) Pathophysiologically, inappropriately elevated aldosterone primarily interacts with widely distributed mineralocorticoid receptors in tissues relevant to CKM syndrome, exacerbating key pathogenic pathways akin to adding fuel to the fire. Building on this synthesis, we emphasize that inappropriately elevated aldosterone is not merely a simple biomarker but an active driver and accelerator of CKM syndrome progression. This review also proposes future directions for integrated PA-CKM screening and management. Incorporating PA into the CKM syndrome framework could not only refine CKM syndrome care but also address the critical underdiagnosis of PA, whose screening rate regrettably remains below 2% in high-risk populations.