Overview
This lecture reviews arterial dissections, focusing on their common features, pathophysiology, cellular mechanisms, genetic influences, and differences between dissection types, alongside risk factors and potential therapeutic targets.
Arterial Dissection Basics
- Arterial dissection is a tear in a major artery wall leading to intramural blood accumulation (hematoma).
- Dissections most often affect large and medium arteries like the aorta, coronary, and cervical arteries.
- Dissections cause severe outcomes depending on location—e.g., stroke, myocardial infarction, or organ failure.
- Intramural hematoma expansion can obstruct blood flow, causing ischemia or infarction.
Arterial Structure & Vulnerability
- Arteries have three layers: intima (endothelial cells), media (smooth muscle & ECM), adventitia (connective tissue).
- Dissections originate in the intima or media but not the adventitia.
- Vasa vasorum (small vessels) supply thick arteries; dysfunction here is linked to dissection risk.
- Sex, age, anatomy, and microenvironment influence arterial vulnerability to dissection.
Key Cellular & ECM Features
- Endothelial cells (ECs) regulate barrier function, blood flow, injury response, and interact with smooth muscle cells.
- Vascular smooth muscle cells (VSMCs) control arterial tone; can switch phenotype from contractile to synthetic in disease, contributing to vessel weakness.
- Extracellular matrix (ECM), mainly elastin and collagen, provides mechanical properties and regulates cell identity; its composition varies by artery, sex, and age.
Genetic & Molecular Pathways in Dissection
- Key pathways implicated: TGF-β signaling, ECM structure, cytoskeleton, and metabolism.
- Mutations in genes like LRP1, collagen (COL1A1, COL3A1, COL4A1, COL5A2), FBN1, and TGF-β receptors are common in arterial dissections.
- Connective tissue disorders (e.g., Marfan, Ehlers-Danlos, Loeys-Dietz) increase dissection risk.
Dissection Types & Features
- Aortic dissection: Most common, associated with hypertension, male sex, and ECM/cytoskeleton gene defects.
- Spontaneous coronary artery dissection (SCAD): Predominantly women aged 45–52; risk factors include hypertension, migraine, and gene variants affecting ECM and TGF-β signaling.
- Cervical artery dissection (CeAD): Can present as stroke in young adults; linked to ECM abnormalities; more frequent in men but occurs at a younger age in women.
- Pulmonary, renal, and visceral artery dissections: Rare; often underdiagnosed, may present with or without intimal tear; genetic studies are limited.
Common Features & Risk Factors
- All dissections involve intramural hematoma (IMH), sometimes with intimal flap.
- Shared risk factors: hypertension, infection/inflammation, migraine, sex, age, and connective tissue disorders.
- Phenotype switching of ECs/VSMCs and ECM remodeling are central mechanisms.
- No specific preventive therapies yet; management often includes antihypertensives (e.g., beta-blockers, losartan).
Key Terms & Definitions
- Arterial dissection — A tear in the artery wall leading to blood accumulation within the vessel wall.
- Intramural hematoma (IMH) — Blood pooling within the arterial wall.
- Extracellular matrix (ECM) — Network of proteins providing structure to vessel walls.
- Vasa vasorum — Small vessels that supply blood to the walls of larger arteries.
- Vascular smooth muscle cell (VSMC) — Muscle cells in the artery wall; regulate vessel tone and can change phenotype.
- Endothelial cell (EC) — Cells forming the artery’s inner lining.
- TGF-β signaling — Cellular pathway important in vessel wall integrity and remodeling.
- Phenotype switching — Change of VSMC or EC from a stable state to a more proliferative or inflammatory state.
Action Items / Next Steps
- Review major genes and pathways implicated in arterial dissections (focus on TGF-β, ECM, cytoskeleton, metabolism).
- Study differences in dissection presentations by location and demographic risk factors.
- Read about current management strategies and potential molecular therapeutic targets for arterial dissections.