Cardiovascular diseases (CVDs) remain a significant global health challenge, with many current treatments addressing symptoms rather than the genetic roots of these conditions. The advent of CRISPR-Cas9 technology has revolutionized genome editing, offering a transformative approach to targeting disease-causing mutations directly. This article examines the potential of CRISPR-Cas9 in the treatment of various CVDs, including atherosclerosis, arrhythmias, cardiomyopathies, hypertension, and Duchenne muscular dystrophy (DMD). The technology’s ability to correct single-gene mutations with high precision and efficiency positions it as a groundbreaking tool in cardiovascular therapy. Recent developments have extended the capabilities of CRISPR-Cas9 to include mitochondrial genome editing, a critical advancement for addressing mitochondrial dysfunctions often linked to cardiovascular disorders. Despite its promise, significant challenges remain, including off-target effects, ethical concerns, and limitations in delivery methods, which hinder its translation into clinical practice. This article also explores the ethical and regulatory considerations surrounding gene editing technologies, emphasizing the implications of somatic versus germline modifications. Future research efforts should aim to enhance the accuracy of CRISPR-Cas9, improve delivery systems for targeted tissues, and ensure the safety and efficacy of treatments in the long term. Overcoming these obstacles could enable CRISPR-Cas9 to not only treat but also potentially cure genetically driven cardiovascular diseases, heralding a new era in precision medicine for cardiovascular health.

CD44, a multi-isoform adhesion receptor for hyaluronic acid (HA), plays a crucial role in regulating cell interactions with the extracellular matrix, cell migration, differentiation, and survival in both physiological and pathological contexts. Accumulating experimental evidence suggests that CD44 is not merely a passive marker of mesenchymal cell activation but rather an active signaling hub driving fibrosis in many organs, including the lung, skin, heart, and liver. Its involvement in fibroblast differentiation into myofibroblasts, as well as induction of the invasive phenotype of these cells, shows striking analogies to the mechanisms of epithelial-to-mesenchymal transition (EMT) known from cancer progression. In this paper, we discuss both the molecular mechanisms of CD44-dependent signaling (including through EGFR, MAPK/ERK, CaMKII, lipid rafts, and Smad) and the influence of its modulation (knockout, antibodies, blockade of HA synthesis) on the course of fibrosis in in vitro and in vivo models. In addition, we present the influence of environmental pollutants—such as heavy metals, particulate matter, endocrine disruptors, and microplastics—on the activation of the HA-CD44 axis in connective tissue, with particular emphasis on their role in the induction of chronic inflammation, EMT, and extracellular matrix deposition. The collected evidence suggests that CD44 serves as a central integrator of inflammatory and fibrogenic signals, and its pharmacological modulation may represent a novel therapeutic strategy for treating fibrotic diseases and chronic inflammatory conditions.