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Common Congenital Heart Lesions - page 32 / 126





32 / 126

32 of 126

*Note that normally the intake of LDL is via LDL receptors on hepatic cells via

negative feedback inhibition…however, because mLDL can’t be taken up by these receptors (LDL receptors), they’re taken up via scavenger receptors on macrophages which aren’t limited by negative feedbackÆfoam cells

2. After entry and modification of LDL, WBCs and SMCs migrate to the vessel wall where they contribute to the formation of the fibrous plaque.

WBC Recruitment

  • WBCs (monocytes & T cells) are recruited as a result of:

    • o

      Natural chemoattractant properties of mLDL

      • o

        Expression of specific cytokines by the endothelium

      • o

        Expression of WBC adhesion molecules on the surface of the injured endothelium, including ICAM-1 & VCAM-1

*Note that mLDL also helps to stimulate ICAM-1 & VCAM-1 expression, illustrating how lipid accumulation helps to promote subsequent inflammation.

  • Once monocytes adhere, penetrate through, and are localized in the subendothelial space, they differentiate into macrophages.

  • The macrophages engulf the mLDL and become foam cells, the main constituent of the fatty streak.

Fatty Streak

  • Represents the earliest visible atherosclerotic lesion

  • Appears as yellow discoloration along the arterial surface

  • Does not protrude into the lumen and thus does not disturb blood flow

  • Present in most individuals by age 20

  • Asymptomatic

  • May regress over time in some locations with exception of the coronary arteries, where they develop into fibrous plaques

  • Although T cells represent only a fraction of the cells within the lesion, their activation typically results in the release of inflammatory cytokines.

SMC Recruitment

  • SMCs normally found in the media layer migrate to the intima, undergo

proliferation, and produce ECM material.

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