Vascular endothelial cell injury: causes, molecular mechanisms, and treatments

Figures

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  FIGURE 1. Regulatory mechanisms of MQC. Under normal conditions, dysfunctional mitochondria can fuse with healthy mitochondria or be cleared through mitophagy to restore intracellular balance. And damaged mitochondria are degraded via mitophagy. mitochondrial biogenesis is triggered as a compensatory response to fission and mitophagy. Under pathological conditions, mitochondrial fission increases, fusion decreases, mitophagy becomes dysregulated, and biogenesis is reduced. This leads to a disruption of the MQC system, resulting in mitochondrial dysfunction and excessive production of ROS. Created with www.biorender.com.

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  FIGURE 2. Inflammation. The process of endothelial damage involves an inflammatory response. Under normal conditions, the activation and inhibition of inflammation are balanced, maintaining vascular stability and monitoring pathogen invasion. In pathological states, endothelial cell injury occurs, leading to disruption of the endothelial barrier. Concurrently, factors such as HMGB1, NF‐κB, and inflammasomes are upregulated, promoting the release of inflammatory cytokines and the adhesion of immune cells to eliminate pathogens. However, this heightened inflammatory state exceeds the regulatory capacity of the system, resulting in further damage to endothelial cells. Created with www.biorender.com.

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  FIGURE 3. Vascular barrier dysfunction. Vascular permeability is dynamically regulated to maintain tissue homeostasis. The functionality of the vascular endothelial barrier is primarily dependent on the integrity of endothelial cell junctions and the glycocalyx. Barrier damage is typically marked by shedding of glycocalyx components and reconstruction of the surface molecules, which promotes the adhesion of leukocytes. Elevated plasma levels of these components can activate TLR‐4, triggering the NF‐κB pathway and promoting the release of proinflammatory cytokines, further exacerbating endothelial cell injury. Moreover, exposure to harmful factors disrupts intercellular junctions, leading to increased vascular leakage and impaired communication between endothelial cells. Created with www.biorender.com.

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  FIGURE 4. Cardiac I/R injury pathogenesis explicated. Following cardiac I/R, microvascular damage involves complex, multifaceted interactions at the molecular, cellular, and tissue levels. Key features include a reduction in eNOS activity and diminished NO production, along with elevated endothelin‐1 (ET‐1) expression, leading to impaired vasodilation. In parallel, damaged endothelial cells increase the expression of adhesion molecules, chemokines, and cytokines, while the production of superoxide anions rises, promoting leukocyte adhesion and rolling, which intensifies inflammation and thrombosis. These pathological changes further exacerbate cardiac I/R injury and contribute to endothelial cell death. Created with www.biorender.com.

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  FIGURE 5. Sepsis pathogenesis explicated. In sepsis, pathogen invasion triggers an excessive production of inflammatory mediators, leading to a cytokine storm, with survivors often entering a paradoxical state of immune suppression. Throughout this process, endothelial cells endure significant damage, including barrier disruption, oxidative stress, mitochondrial dysfunction, and phenotypic changes. These injuries drive coagulopathy, uncontrolled inflammation, and increased vascular permeability. The breakdown of endothelial function typically signals the onset of multiple organ dysfunction syndrome (MODS). Created with www.biorender.com.

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  FIGURE 6. Diabetic vascular injury explicated. Diabetic vascular injury involves the cardiac, cerebral, renal, ophthalmic and peripheral systems. The mechanisms are complex, hyperglycemia and insulin resistance contribute to mitochondrial dysfunction, oxidative stress, and disruptions in metabolic pathways, including the formation of AGEs and activation of the PKC pathway. These interconnected processes work synergistically, ultimately leading to vascular remodeling and functional impairment. Created with www.biorender.com.