Samir Bolivar

Cardiac fibrosis is a major pathological feature of several cardiovascular diseases and is characterized by excessive extracellular matrix deposition, leading to ventricular stiffening, impaired cardiac function, and ultimately heart failure. Despite its substantial clinical burden, therapies specifically targeting the fibrotic process remain limited. Irisin, a myokine generated by cleavage of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a cardioprotective factor with potential antifibrotic properties. This review critically examines current evidence on the molecular mechanisms underlying the cardioprotective and antifibrotic effects of irisin, with particular emphasis on integrin αVβ5, AMP-activated protein kinase (AMPK), and their associated signaling pathways. Preclinical studies indicate that irisin engages context-dependent signaling mechanisms that vary according to cell type and pathological setting. These include integrin αVβ5-dependent activation of AMPK or AKT, modulation of oxidative and nitrosative stress, inhibition of ferroptosis through SIRT1/p53 signaling, attenuation of NLRP3 inflammasome activation, preservation of mitochondrial homeostasis, activation of Nrf2-dependent antioxidant responses, and suppression of TGF-β1/Smad2/3-mediated fibroblast activation. Across experimental models, these molecular effects are associated with reduced fibroblast activation and extracellular matrix accumulation, improved mitochondrial and redox homeostasis, and attenuation of pathological cardiac remodeling. Collectively, current evidence identifies irisin as a multifaceted regulator of pathological cardiac remodeling with potential relevance to the attenuation of cardiac fibrosis. However, the available evidence remains predominantly preclinical, and substantial uncertainties regarding receptor and pathway specificity, pharmacokinetics, optimal delivery, safety, and therapeutic efficacy must be resolved before clinical translation.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, creating the need for new therapeutic strategies targeting the pathological processes involved. Mitochondria, which comprise one-third of cardiac cell volume, maybe a potential therapeutic target for CVD. Known primarily for energy production, mitochondria are also involved in other processes including intermediary metabolism, mitophagy, calcium homeostasis, and regulation of cell apoptosis. Mitochondrial function is closely linked to morphology, which is altered through mitochondrial dynamics, including processes such as fission and fusion, which ensure that the energy needs of the cell are met. Recent data indicate that mitochondrial dysfunction is involved in the pathophysiology of several CVDs, including cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and cardiac fibrosis. Furthermore, mitochondrial dysfunction is associated with oxidative stress related to atherosclerosis, hypertension, and pulmonary hypertension. In this review, we first briefly present the physiological mechanisms of mitochondrial function in the heart and then summarize the current knowledge on the impact of mitochondrial dysfunction on CVD. And finally, we highlight the evidence from in vitro, in vivo, and clinical studies of the cardioprotective effects of drugs that preserve mitochondrial function in CVD. It is hoped that this review may provide new insights into the need to discover new pharmacological targets with direct actions on mitochondria that may provide combined therapeutic strategies to optimally treat these pathologies.

ARTICLE INFORMATION Title: Identification of Epigenetic Regulators of Fibrotic Transformation in Cardiac Fibroblasts Through Bulk and Single-Cell CRISPR Screens Authors: Laura Pilar Aguado Álvaro et al. Date: April 23, 2025 Reviewer: [SJBG] EVAL...

Cardiac fibrosis (CF) is characterized by the excessive deposition of collagen types I (COI I) and III (COI III), primarily mediated by cardiac fibroblasts (CFB). Recent advances in epigenetic research have enhanced our understanding of the molecular mechanisms underlying CF and have facilitated the identification of novel therapeutic strategies targeting key proteins and signaling pathways involved in its progression. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), are structural and chemical alterations that regulate gene expression and cellular responses without changing the DNA sequence. Investigating the role of epigenetic enzymes in CF may reveal promising pharmacological targets. This review summarizes current evidence on epigenetic modifications implicated in CF and discusses their potential as therapeutic targets for modulating this pathological process.

Cardiac fibrosis is known as the expansion of the cardiac interstitium through excessive deposition of extracellular matrix proteins; this process is performed by a multifunctional cell known as the cardiac fibroblast. After the myocardial injury, these cells are activated as a repair program, increase, and switch to a contractile phenotype, which is evidenced by an increase in alpha- smooth muscle actin. Likewise, there is an increase in type I and III collagen, which are considered profibrotic biomarkers. It is believed that one of the proteins involved in cardiac remodeling is METTL3, which is the enzyme responsible for N6-methyladenosine (m6A) methylation, the most common and abundant epigenetic modification of eukaryotic mRNA. This review focuses on recent studies in which the possible role of METTL3 in the progression of fibrosis has been demonstrated, mainly in cardiac fibrogenesis.

The search for new drugs with the potential to ensure therapeutic success in the treatment of cardiovascular diseases has become an essential pathway to follow for health organizations and committees around the world. In June 2021, the World Health Organization listed cardiovascular diseases as one of the main causes of death worldwide, representing 32% of them. The most common is coronary artery disease, which causes the death of cardiomyocytes, the cells responsible for cardiac contractility, through ischemia and subsequent reperfusion, which leads to heart failure in the medium and short term. Metformin is one of the most-used drugs for the control of diabetes, which has shown effects beyond the control of hyperglycemia. Some of these effects are mediated by the regulation of cellular energy metabolism, inhibiting apoptosis, reduction of cell death through regulation of autophagy and reduction of mitochondrial dysfunction with further reduction of oxidative stress. This suggests that metformin may attenuate left ventricular dysfunction induced by myocardial ischemia; preclinical and clinical trials have shown promising results, particularly in the setting of acute myocardial infarction. This is a review of the molecular and pharmacological mechanisms of the cardioprotective effects of metformin during myocardial ischemia-reperfusion injury.

Objective: to characterize the pharmacotherapy of patients with acute ischemic stroke (ACVi) treated with recombinant tissue plasminogen activator (rt-PA) in a hospital in Soledad - Atlántico in the period 2015-2020. Materials and methods: a retrospective descriptive observational study was carried out, for the quantitative variables the Kolmogórov – Smirnov normality test was applied. The data that complied with the assumption of normality (p>0.05) were presented as means ± standard deviation, those that did not comply were presented as medians. Categorical variables were shown as frequencies or percentages. Results: 72 patients with a median age of 74 years were studied, 52.2% of the population were men, 69.4% suffered from arterial hypertension, 26.4% received platelet aggregation inhibitors, excluding heparin, and 23, 6% were administered drugs belonging to the therapeutic group of heparins. Twenty-five percent of the population developed hemorrhage: 19.4% had intracerebral hemorrhage, 4.2% developed subarachnoid hemorrhage, and 1.4% had gastrointestinal hemorrhage. Conclusion: it was possible to identify opportunities for improvement in the management of patients with stroke and in the use of alteplase. A higher percentage of bleeding complications was found compared to studies previously conducted in Colombia. Further investigations are required to corroborate the results, due to the limited number of participants and scarce data related to clinical histories.

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.

Las enfermedades cardiovasculares (ECV) son un conjunto de trastornos del corazón y de los vasos sanguíneos, que constituyen la principal causa de mortalidad en el mundo. En la búsqueda de alternativas para esta problemática, plantas medicinales de la familia Euphorbiaceae, han sido empeladas con fines terapéuticos, para prevenir, atenuar o curar los efectos generados por estas enfermedades. El objetivo de este trabajo fue conocer el perfil fitoquímico y evaluar la actividad anticoagulante in vitro de los extractos etanólicos de las hojas de Croton malambo y Acalypha hispida sobre plasma humano. Para ello, se obtuvo el extracto de las hojas y se le realizó el tamizaje fitoquímico, la evaluación del Tiempo de Tromboplastina Parcial activada (TTPa) y del Tiempo de Protombina (TP). En el perfil fitoquímico, se confirmó la presencia de alcaloides, taninos, flavonoides, leucoantocianidinas, fenoles, sesquiterpenlactonas, glucósidos cardiotónicos y terpenos. En la actividad anticoagulante, se evidenció la inhibición de la coagulación en la vía intrínseca, obteniendo resultados significativos para el TTPa, a diferencia que el test TP, donde los resultados obtenidos se encontraron similares al control. Esta investigación demuestra la acción anticoagulante de las plantas, ya que induce, significativamente, a una mayor prolongación del tiempo de coagulación; ambas especies presentaron una mayor actividad, a 200 mg/mL.