Immune Vascular Inflammation and Atherosclerosis

What acute inflammation accomplishes

Inflammation allows inflammatory cells, plasma proteins, and fluid to leave blood vessels and enter interstitial tissue. Acute inflammation is an immediate innate response to infection or tissue necrosis and is characterized by tissue neutrophils and edema.

The vascular phase

Acute inflammation produces vasodilation and increased vascular permeability. As fluid leaves vessels, blood viscosity rises and flow slows, allowing neutrophils to marginate along the vascular surface.

Innate recognition starts mediator production

Toll-like receptors on macrophages and dendritic cells recognize shared microbial patterns. Their activation upregulates NF-κB, which activates immune-response genes and drives production of multiple inflammatory mediators.

Vascular mediators explain the cardinal findings

Histamine promotes vasodilation and endothelial contraction. Prostaglandins promote vasodilation, while PGE₂ sensitizes sensory nerve endings. Bradykinin promotes vasodilation, permeability, and pain. Together these effects explain redness, warmth, swelling, and pain.

Atherosclerosis is an intimal plaque disease

Atherosclerosis is an intimal plaque process in large and medium-sized arteries. The plaque contains a necrotic lipid core, mostly cholesterol, beneath a fibromuscular cap and can obstruct blood flow.

Endothelial dysfunction begins the sequence

Endothelial dysfunction permits macrophage and LDL accumulation in the intima. Macrophages take up oxidized lipid through scavenger receptors and become foam cells, producing the fatty streak that precedes a mature plaque.

Smooth muscle converts streak to plaque

Inflammation is central to progression from fatty streak to fibrous plaque. Smooth-muscle cells migrate and proliferate, then deposit extracellular matrix; the resulting fibrous plaque can progress to a complex, calcified atheroma.

Major risk-factor groups

Modifiable risks are:

Hypertension. Smoking. Dyslipidemia. Diabetes. Nonmodifiable risks are:

Age. Male sex or postmenopausal status. Family history. LDL increases risk while HDL decreases it.

Stable and vulnerable plaques

Plaque Cap Lipid core Inflammation Behavior Stable Dense Small Less Chronic ischemia Vulnerable Thin Large Dense Rupture, thrombosis, or embolization

Why the aorta matters

The abdominal aorta is the most common location listed for atherosclerosis. Plaque-related weakening of the vessel wall can produce an aneurysm, while plaque rupture can release cholesterol-containing atherosclerotic emboli.

Stenosis, rupture, and embolization

Stenosis reduces blood flow and produces ischemia. Plaque rupture with thrombosis can cause myocardial infarction or stroke. Plaque rupture with embolization produces emboli containing cholesterol crystals.