What is the role of endothelial injury in the etiology of coronary artery atherosclerosis?

Updated: Apr 09, 2021
  • Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Yasmine S Ali, MD, MSCI, FACC, FACP  more...
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In his response-to-injury hypothesis, Ross postulated that atherosclerosis begins with endothelial injury, making the endothelium susceptible to the accumulation of lipids and the deposition of thrombus. The mechanisms of atherogenesis remain uncertain, but the response-to-injury hypothesis is the most widely accepted proposal.

In the 1990s, Ross and Fuster proposed that vascular injury starts the atherosclerotic process. [8] Such injuries can be classified as follows:

  • Type I - Vascular injury involving functional changes in the endothelium, with minimal structural changes, (ie, increased lipoprotein permeability and white blood cell adhesion)

  • Type II - Vascular injury involving endothelial disruption, with minimal thrombosis

  • Type III - Vascular injury involving damage to media, which may stimulate severe thrombosis, resulting in unstable coronary syndromes

According to the response-to–vascular injury theory, injury to the endothelium by local disturbances of blood flow at angulated or branch points, along with systemic risk factors, perpetuates a series of events that culminate in the development of atherosclerotic plaque.

As discussed in greater detail below, endothelial damage occurs in many clinical settings and can be demonstrated in individuals with dyslipidemia, hypertension, diabetes, advanced age, nicotine exposure, and products of infective organisms (ie, Chlamydia pneumoniae). Damage to the endothelium may cause changes that are localized or generalized and that are transient or persistent, as follows:

  • Increased permeability to lipoproteins

  • Decreased nitric oxide production

  • Increased leukocyte migration and adhesion

  • Prothrombotic dominance

  • Vascular growth stimulation

  • Vasoactive substance release

Endothelial dysfunction is the initial step that allows diffusion of lipids and inflammatory cells (ie, monocytes, T lymphocytes) into the endothelial and subendothelial spaces. Secretion of cytokines and growth factors promotes intimal migration, SMC proliferation, and accumulation of collagen matrix and of monocytes and other white blood cells, forming an atheroma. More advanced atheromas, even though nonocclusive, may rupture, thus leading to thrombosis and the development of ACS and MI.

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