Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets DOI
Israel O. Bolanle,

Gaetan C. de Liedekerke Beaufort,

Peter D. Weinberg

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Transport of LDL (low-density lipoprotein) from plasma to arterial intima is thought be rate limiting in the development atherosclerosis. Its variation likely determines where lesions develop within arteries and might account for some currently unexplained difference disease susceptibility between individuals. It may also critical lipid-rich, unstable plaques. Mechanisms have been controversial but recent evidence suggests that caveolar transcytosis across endothelial cells dominant pathway. Receptors involved are LDLR (LDL receptor), SR-B1 (scavenger receptor class B type 1), ALK1 (activin receptor-like kinase 1). The role influenced by IL-1β (interleukin-1β); HDL (high-density lipoprotein), DOCK4 (dedicator cytokinesis 4), GPER (G-protein–coupled estrogen HMGB1 (high mobility group box 1); BMP (bone morphogenetic protein) 9. Additionally, BMP4 stimulates transcytosis, FSTL1 (follistatin-like 1 inhibits it. Fundamental transcytotic mechanisms include caveola formation, undocking, trafficking, docking; they cholesterol-lowering agents, MYDGF (myeloid-derived growth factor), MFSD2a (major facilitator superfamily domain containing 2a; blood-brain barrier), inhibitors dynamin-2 tubulin polymerization. relative merits different therapeutic approaches discussed, with statins, colchicine, benzimidazoles, metformin being existing drugs repurposed salidroside glycyrrhizic acid nutraceuticals worth investigating. Finally, we discuss against ferry-boat model contributions receptor-mediated, fluid-phase, active inhibition most beneficial.

Language: Английский

Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets DOI
Israel O. Bolanle,

Gaetan C. de Liedekerke Beaufort,

Peter D. Weinberg

et al.

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Transport of LDL (low-density lipoprotein) from plasma to arterial intima is thought be rate limiting in the development atherosclerosis. Its variation likely determines where lesions develop within arteries and might account for some currently unexplained difference disease susceptibility between individuals. It may also critical lipid-rich, unstable plaques. Mechanisms have been controversial but recent evidence suggests that caveolar transcytosis across endothelial cells dominant pathway. Receptors involved are LDLR (LDL receptor), SR-B1 (scavenger receptor class B type 1), ALK1 (activin receptor-like kinase 1). The role influenced by IL-1β (interleukin-1β); HDL (high-density lipoprotein), DOCK4 (dedicator cytokinesis 4), GPER (G-protein–coupled estrogen HMGB1 (high mobility group box 1); BMP (bone morphogenetic protein) 9. Additionally, BMP4 stimulates transcytosis, FSTL1 (follistatin-like 1 inhibits it. Fundamental transcytotic mechanisms include caveola formation, undocking, trafficking, docking; they cholesterol-lowering agents, MYDGF (myeloid-derived growth factor), MFSD2a (major facilitator superfamily domain containing 2a; blood-brain barrier), inhibitors dynamin-2 tubulin polymerization. relative merits different therapeutic approaches discussed, with statins, colchicine, benzimidazoles, metformin being existing drugs repurposed salidroside glycyrrhizic acid nutraceuticals worth investigating. Finally, we discuss against ferry-boat model contributions receptor-mediated, fluid-phase, active inhibition most beneficial.

Language: Английский

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