CORRESPONDENCE: LETTER TO THE EDITOR
Arterial Microvessels: An Early or Late Sign of Atherosclerosis?
Barbara C. Biedermann, MD,
Blai Coll, MD, PhD,
Dan Adam, PhD and
Steve B. Feinstein, MD, FACC*
* Department of Internal Medicine, Section of Cardiology, Rush University Medical Center, Chicago, Illinois 60612 (Email: sfeinste{at}rush.edu).
Hypoxia is a strong stimulus for the induction of angiogenesis. In an elegant series of experiments, including in vivo labeling of hypoxic tissues, Sluimer et al. (1) have demonstrated that hypoxia in advanced atherosclerotic plaques colocalized with the expression of hypoxia-induced transcription factors (i.e., HIF1 , HIF2), growth factors (i.e., vascular endothelial growth factor), and glucose transporters (i.e., GLUT1, GLUT3) and that all these microenvironmental changes were accompanied by neovascularization—the number of microvessels per mm2 intima area was significantly greater in advanced than in early atherosclerotic lesions.
We have previously shown that 2 distinctive angiogenic events occur during atherosclerosis in humans (2). In addition to ectopic plaque neovascularization, we found a hyperplastic network of vasa vasorum in the arterial adventitia in early lesions of patients with active, symptomatic disease. However, the arterial adventitia is a physiologically vascularized compartment of the arterial wall and is not expected to harbor a hypoxic microenvironment. Studies based on swine models of hypercholesterolemia showed that adventitial neovascularization is not exclusively related to plaque formation; those animals presented with the highest vasa vasorum count but without any arterial wall thickening (3). The authors suggested that the main stimulus to vessel wall neovascularization might not be local hypoxia but could rather be related to the increased oxidative stress.
However, Sluimer et al. (1) showed that metabolically active macrophages may contribute to tissue hypoxia by oxygen exhaustion (4) and that this mechanism could also contribute to hyperplasia of vasa vasorum in the arterial adventitia. Because contrast-enhanced transcutaneous ultrasound is a bedside procedure that can be used to visualize both plaque (5) and adventitial microvessels (6), the 2 compartments might be accessible for the diagnosis of early and late stages of preclinical atherosclerosis. A common pathogenic mechanism might eventually be targeted therapeutically.
 |
Footnotes
|
|---|
Please note: Dr. Feinstein has received speaker's honorarium from Takeda, Merck, Abbott, and GE Healthcare; and research funding from Takeda.
|
References
|
|---|
- Sluimer JC, Gasc JM, van Wanroij JL, et al. Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis J Am Coll Cardiol 2008;51:1258-1265.[Abstract/Free Full Text]
- Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis Circulation 2004;110:2843-2850.[CrossRef][ISI][Medline]
- Versari D, Gossl M, Mannheim D, et al. Hypertension and hypercholesterolemia differentially affect the function and structure of pig carotid artery Hypertension 2007;50:1063-1068.[Abstract/Free Full Text]
- Mayr M, Sidibe A, Zampetaki A. The paradox of hypoxic and oxidative stress in atherosclerosis J Am Coll Cardiol 2008;51:1266-1267.[Free Full Text]
- Shah F, Balan P, Weinberg M, et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med 2007;12:291-297.[Abstract/Free Full Text]
- Adam D, Soqulin A, Coll B, et al. Quantitative contrast-enhanced ultrasound imaging of the carotid artery vasa vasorum: calibration and initial results(abstr) J Am Coll Cardiol 2008;51(Suppl A):A318.
Related Article
-
Reply
- Judith C. Sluimer, Ann-Pascale J. Bijnens, and Mat J. Daemen
J. Am. Coll. Cardiol. 2008 52: 968-969.
[Full Text]
[PDF]
|
Top
References