Figure 1.

Endothelium and CVDs. Different mechanisms leading to leaky vasculature, increased inflammation, plaque development, or apoptosis in CVDs. The figure provides a detailed depiction of the interconnected mechanisms within endothelial dysfunction and their relevance to CVDs. It illustrates how the endothelium plays a crucial role in the pathogenesis of CVDs through various processes. The sequence begins with endothelial dysfunction leading to a leaky vasculature and increased vascular permeability, facilitated by TLR4 activation of the NF-κB pathway, upregulation of ICAM-1, VCAM-1, Selectins and subsequent cytokine release—all contributing to heightened inflammation. This cascade of events culminates in inflammation, affecting claudin-1 and ZO-1. The progression of inflammation exacerbates plaque development through the transformation of macrophages into foam cells, releasing pro-inflammatory cytokines, including IL-6, TNF-α, and MMP-7. Reduced phagocytosis and decreased CD163 expression highlight the impact of these processes on plaque instability within the vasculature. Additionally, upregulated vWF mediates endothelial activation and platelet adhesion, crucial for the inflammatory response. Moreover, vWF facilitates immune cell recruitment and acts as a signaling molecule, amplifying the inflammatory cascade. Plaque formation and rupture are highlighted as critical events triggered by endothelial dysfunction and oxLDL accumulation, contributing to the progression of CVDs. Finally, the figure illustrates apoptosis induced by various factors such as oxidative stress, hypoxia, reduced NO, ER stress, and chemotherapeutic agents and shear stress (as shown by red arrows pointing in the same direction, while others veer left or right, and some proceeding straight, capturing the dynamic nature of biomechanical forces acting on the endothelium). These factors contribute to apoptotic cell death within the vascular environment, emphasizing the diverse mechanisms through which endothelial dysfunction can lead to adverse outcomes in cardiovascular health, ultimately impacting the development and progression of various CVDs. TLR4: Toll-like Receptor 4, ICAM-1: Intercellular Adhesion Molecule-1, VCAM-1: Vascular Cell Adhesion Molecule-1, NF-κB: Nuclear Factor Kappa B, IL-6: Interleukin-6, TNF-α: Tumor Necrosis Factor- α, MMP-7: Matrix Metalloproteinase-7, CD163: Cluster of Differentiation 163, vWF: von Willebrand Factor, NO—Nitric Oxide, ER—Endoplasmic Reticulum, oxLDL: Oxidized Low-Density Lipoprotein, ZO-1: Zonula Occludens-1, EndMT: Endothelial-to-Mesenchymal Transition.