Three-Layer Architecture · Intima / Media / Adventitia
Vascular Wall Structure
Vessel wall composition determines mechanical properties — elastic arteries buffer pulsatile flow; muscular arteries distribute and regulate flow to organs.
| Layer | Composition | Function | Disease Relevance |
|---|---|---|---|
| Tunica Intima | Single endothelial monolayer (VE-cadherin junctions) + subendothelial connective tissue + internal elastic lamina (IEL — fenestrated elastin) | Antithrombotic surface (eNOS/NO, PGI₂, thrombomodulin, TFPI); permeability barrier; shear stress sensing | Endothelial injury → LDL subendothelial retention → foam cells → fatty streak → plaque |
| Tunica Media | Vascular smooth muscle cells (VSMCs) + elastic laminae (elastin) + collagen (type I/III) + proteoglycans; thickness proportional to pressure | Vasoconstriction/vasodilation (α1/β2 adrenergic, angiotensin II AT1R, NO/cGMP, ETₐR/endothelin); blood pressure regulation; Windkessel elastic recoil | VSMC phenotypic switching (contractile → synthetic) drives plaque stability; medial calcification (Mönckeberg) in diabetes/CKD |
| Tunica Adventitia | Fibroblasts + type I collagen (large bundles) + vasa vasorum (microvessels supplying wall) + nerve endings (adrenergic/cholinergic) + external elastic lamina (EEL) | Structural scaffolding; neural control; oxygen/nutrient supply to outer wall via vasa vasorum; macrophage/lymphocyte surveillance | Vasa vasorum angiogenesis into plaque → intraplaque haemorrhage → unstable angina |
Windkessel Effect — Elastic Arteries (Aorta, Pulmonary Artery)
Cardiac systole: LV ejects ~70 mL stroke volume at peak pressure ~120 mmHg
↓
Elastic aorta DISTENDS (stores kinetic energy in elastic wall)
↓
Systolic peak is BUFFERED → reduces cardiac afterload
↓
Cardiac diastole: Aortic wall RECOILS (releases stored energy)
↓
Maintains diastolic pressure ~80 mmHg → continuous tissue perfusion
Windkessel compliance C = ΔV / ΔP
Elastic arteries: high C → smooth pressure wave propagation
Stiffened arteries (ageing, hypertension): low C → ↑ pulse pressure,
↑ systolic pressure, ↑ LV afterload → LVH → HFpEF
Pulse wave velocity (PWV) = √(Eh/2rρ) [Moens-Korteweg]
Normal aortic PWV: ~5–7 m/s; stiff: >10 m/s
PWV is an independent predictor of CV mortality
Endothelial Mechanosensing — Shear Stress Axis
Wall shear stress τ = 4ηQ / πr³ [Poiseuille]
Laminar high shear (atheroprotective):
KLF2/KLF4 → eNOS↑ → NO → vasodilation + anti-inflammatory
Nrf2 → HO-1/ferritin → antioxidant
Flow-aligned endothelium → intact junctions → low permeability
Disturbed low shear (atheroprone — bifurcations, curvatures):
NF-κB activation → VCAM-1/ICAM-1/E-selectin → monocyte recruitment
Ox-LDL uptake → foam cell formation → fatty streak
eNOS uncoupling (BH4 depletion) → O₂•⁻ production
Vasoregulation
Endothelium-dependent and independent mechanisms controlling lumen diameter
| Mediator | Source | Receptor / Pathway | Effect |
|---|---|---|---|
| Nitric oxide (NO) | Endothelium (eNOS) | sGC → cGMP → PKG → MLCP, BKCa | Vasodilation; inhibits platelet aggregation |
| Prostacyclin (PGI₂) | Endothelium (COX/PGIS) | IP receptor → cAMP → PKA | Vasodilation; anti-aggregant |
| Endothelin-1 (ET-1) | Endothelium | ETₐR (VSMC) → Gq → Ca²⁺/MLCK | Potent vasoconstriction; proliferation |
| Angiotensin II | ACE (endothelial) from Ang I | AT1R → Gq → IP₃/Ca²⁺ + MAPK | Vasoconstriction; VSMC growth; aldosterone release |
| Norepinephrine | Sympathetic nerve terminals | α1-AR → Gq → PLC → IP₃/DAG | Vasoconstriction (resistance arteries) |
| Adenosine | Metabolically active tissue | A2A/A2B → cAMP | Arteriolar vasodilation (autoregulation) |
Pathology
Atherosclerosis, hypertension, aneurysm, arterial stiffness
Atherosclerosis — Pathogenesis
Response-to-retention hypothesis: disturbed shear → endothelial activation → LDL transcytosis and retention in intima → oxidised LDL → TLR4 activation → MCP-1/CCL2 → monocyte recruitment → macrophage differentiation → foam cells (lipid-laden, CD36/SR-A mediated uptake) → fatty streak. Plaque progression: SMC migration from media (PDGF, TGF-β), collagen cap formation, fibrous plaque. Plaque rupture at thin fibrous cap → thrombosis (ACS).
Hypertension — Vascular Remodelling
Sustained ↑ BP → VSMC hypertrophy/hyperplasia (Ang II, ET-1) → media thickening → increased wall:lumen ratio. Elastic artery stiffening (cross-linking of elastin, collagen accumulation) → ↑ pulse wave velocity → ↑ systolic pressure → LVH. Target organ damage: LVH, renal afferent arteriosclerosis (hyalinosis), retinal arteriovenous nicking (AV nipping).
Aortic Aneurysm
MMP-2/MMP-9 (from macrophages, VSMCs) degrade elastin and collagen in the media → loss of structural integrity → progressive dilation. AAA: >3 cm aortic diameter; rupture risk markedly increases >5.5 cm. Risk: smoking (strongest), hypertension, male sex, FBN1/FBN2 mutations (Marfan); thoracic aortic aneurysm linked to VSMC α-actin (ACTA2) and myosin heavy chain (MYH11) mutations.
Arterial Stiffness
Loss of elastin (fragmented with age), advanced glycation end-product cross-linking of collagen, medial calcification → progressive stiffening. Central arterial stiffness (aortic PWV >10 m/s) independently predicts CV mortality. Treatment: antihypertensives (ACEi, ARBs) partially reduce progression; RAAS inhibition shown to reduce aortic PWV in hypertensive patients.
Vasculitides
Giant cell arteritis (GCA): granulomatous inflammation of medium/large vessels (temporal artery, aorta); giant cells, VSMC destruction; ↑ ESR, CRP; JAK inhibitors (tocilizumab, IL-6 inhibition) reduce relapse. Takayasu arteritis: granulomatous aortitis in young women; ↑ aortic PWV; immunosuppression + anti-TNF.
Atlas Connections
- Libby P et al. (2019). Atherosclerosis. Nat Rev Dis Primers 5:56. doi:10.1038/s41572-019-0106-z
- Laurent S et al. (2006). Expert consensus document on arterial stiffness. Eur Heart J 27(21):2588–2605.
- Gimbrone MA Jr & García-Cardeña G (2016). Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 118(4):620–636.
- Fung YC (1993). Biomechanics: Mechanical Properties of Living Tissues. Springer-Verlag, 2nd ed.
- Dzau VJ et al. (2006). The vascular renin-angiotensin system in health and disease. J Renin Angiotensin Aldosterone Syst 7(1):3–9.