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Common Congenital Heart Lesions - page 31 / 126

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  • 2.

    Describe the pathological lesion of atherosclerosis in the arterial wall

    • Considered a chronic, inflammatory process, atherogenesis (the formation of an

athersclerotic fibrous plaque) involves 3 key steps:

    • 1.

      Accumulation of lipids within the intima

    • 2.

      Recruitment of WBCs and SMCs to the vessel wall

    • 3.

      ECM deposition

  • 1.

    For lipids to accumulate in the intimal layer there must be some sort of

breakdown in endothelial function.

  • Refer to Table 5.1 (p. 113) for a good compare/contrast of normal vs. abnormal

endothelial function!

Factors causing endothelial dysfunction:

  • Physical Forces: These are typically created in arterial branch points, where laminar flow is disrupted. As a compensatory mechanism, the endothelium will typically express enzymes responsible for production of NO and superoxide dismutase, whose normal, atheroprotective function is subsequently altered as a result of the disturbed flow.

  • Toxic chemical environment exposure: This includes smoking, dyslipidemia, and diabetes. These states, among other things, may lead to an increase in the production of reactive oxygen species by endothelial cells.

*In general, these factors can lead to endothelial dysfunction by:

    • o

      Impairing the endothelial permeability barrier function

      • o

        Release of inflammatory cytokines by the endothelium

      • o

        Increased expression of WBC adhesion molecules

      • o

        Aberrant release of vasoactive chemicals (ie. prostacyclin & NO)

      • o

        Interference with endothelial antithrombotic properties

  • With the endothelium no longer serving as an effective barrier, lipoproteins like LDL (transporters of fat in the blood) are able to penetrate the intima and accumulate in the subendothelial space.

  • LDL undergoes biochemical modifications (ie. oxidation)ÆmLDL

  • mLDL has major consequences that include:

    • o

      Recruitment of monocytes to the vessel wall

  • o

    Increased endothelial expression of inflammatory mediators (ie. M-CSF)

    • o

      Ingestion of mLDL by macrophages via scavenger receptorsÆfoam cells

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