Krüppel-like factors (KLFs) are a set of DNA-binding proteins belonging to a family of zinc-finger transcription factors, which have been associated with many biological processes related to the activation or repression of genes, inducing cell growth, differentiation, and death, and the development and maintenance of tissues. In response to metabolic alterations caused by disease and stress, the heart will undergo cardiac remodeling, leading to cardiovascular diseases (CVDs). KLFs are among the transcriptional factors that take control of many physiological and, in this case, pathophysiological processes of CVD. KLFs seem to be associated with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss of functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of the differentiation of cardiac myofibroblasts or a modified fatty acid oxidation related to the formation of a dilated cardiomyopathy, myocardial infarctions, left ventricular hypertrophy, and diabetic cardiomyopathies. In this review, we describe the importance of KLFs in cardiovascular diseases such as atherosclerosis, myocardial infarction, left ventricle hypertrophy, stroke, diabetic cardiomyopathy, and congenital heart diseases. We further discuss microRNAs that have been involved in certain regulatory loops of KLFs as they may act as critical in CVDs.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

Background: Myocardial infarction triggers a complex remodeling process involving inflammation, hypertrophy, fibrosis, and electrical adaptation, ultimately predisposing the heart to failure. Krüppel-like factors (KLFs) are transcriptional regulators implicated in cardiovascular development and disease; however, a comprehensive temporal characterization of their coordinated activity during post-injury remodeling remains lacking. Objective: To define the temporal orchestration of the KLF family during myocardial injury and hypertrophy, and to integrate these dynamics within regulatory networks associated with cardiac remodeling. Methods: Myocardial injury was induced in rats using intraperitoneal isoproterenol. Left ventricular tissue was collected over a 21-day period. Cardiac morphometry, histology, immunohistochemistry, and quantitative gene expression analyses were performed to evaluate structural and transcriptional changes. Publicly available human cardiac and fibroblast datasets were analyzed for translational comparison, and protein–protein interaction networks were constructed to identify functional associations. Results: Isoproterenol treatment induced progressive hypertrophy, structural disorganization, and sustained fibrotic remodeling. KLFs displayed coordinated, phase-specific regulation, characterized by early activation of inflammation-associated members, intermediate engagement of factors linked to transforming growth factor signaling and hypertrophy modulation, and late induction of regulators associated with apoptosis and scar formation. These temporal patterns paralleled changes in inflammatory mediators, cardiac transcription factors, and genes involved in electrical and calcium handling pathways. Human expression analyses supported tissue-specific specialization of key KLFs. Conclusions: KLFs exhibit a coordinated and temporally structured regulatory program during myocardial remodeling, functioning as a transcriptional network that integrates inflammation, fibrosis, hypertrophy, and electrical adaptation. These findings position KLFs as key regulatory nodes in cardiac remodeling and potential targets for therapeutic intervention.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.