Endothelium: Structure, Function & Importance for Health

The endothelium is a monolayer of endothelial cells lining the entire cardiovascular system (heart, arteries, veins, capillaries, lymphatics) — ~1–6 trillion cells, ~1 kg mass, surface area ~4,000–7,000 m².

Key Functions

1. Selective Barrier: Regulates passage of fluids, solutes, cells (leukocyte trafficking). Tight junctions (continuous), fenestrations (kidney, gut), discontinuous (liver sinusoids).
2. Vascular Tone Regulation: Synthesizes NO (vasodilation), prostacyclin (PGI₂), endothelin-1 (vasoconstriction). Balances perfusion.
3. Antithrombotic Surface: Heparan sulfate (antithrombin cofactor), thrombomodulin (protein C activation), TFPI, NO/PGI₂ (inhibit platelet adhesion). Prevents clotting.
4. Angiogenesis: VEGF, FGF signaling → sprouting, tube formation, maturation. Critical in development, wound healing, tumor growth.
5. Inflammation Modulation: Adhesion molecules (selectins, ICAM-1, VCAM-1) recruit leukocytes. Pro/anti-inflammatory cytokines.
6. Metabolic & Hormonal: Lipoprotein lipase, ACE (angiotensin II), insulin transport, ANP clearance.

Endothelial Dysfunction

Early marker of atherosclerosis. Features: reduced NO, oxidative stress, pro-inflammatory/pro-thrombotic phenotype. Driven by: hypertension, diabetes, smoking, dyslipidemia, obesity, inactivity.

Clinical Relevance

• Coronary artery disease, stroke, PAD, CKD, erectile dysfunction.
• Assessed by flow-mediated dilation (FMD), biomarkers (ADMA, vWF, E-selectin).
• Improved by exercise, Mediterranean diet, statins, ACEi/ARB, SGLT2i, smoking cessation.

Endothelial health = vascular health = systemic health.