A major role for VCAM-1, but not ICAM-1, in early atherosclerosis

Cybulsky, Myron I.; Iiyama, Kaeko; Li, Hongmei; Zhu, Shudong; Chen, Mian; Iiyama, Motoi; Davis, Vannessa; Gutierrez-Ramos, José-Carlos; Connelly, Philip W.; Milstone, David S.

doi:10.1172/jci11871

Cited by 1,060 publications

(803 citation statements)

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“…Vascular smooth muscle cells and ECs are the two main cell types involved in vascular homoeostasis 25, 26. The inflammatory environment activates VCAM‐1 expression on ECs, thereby allowing for leucocyte adhesion and infiltration in inflamed tissue 27, 28. In our study, VCAM‐1 mRNA expression in the mouse aorta was precociously increased with cCII immunization.…”

Section: Discussionsupporting

confidence: 50%

Aortic VCAM‐1: an early marker of vascular inflammation in collagen‐induced arthritis

Denys

Clavel

Lemeiter

et al. 2016

J Cellular Molecular Medi

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Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen‐induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen‐induced arthritis was induced with intradermal injection of chicken type‐II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule‐1 (VCAM‐1), inducible nitric oxide synthase (iNOS) and interleukin‐17 were analysed by quantitative RT‐PCR. Vascular cell adhesion molecule‐1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen‐induced arthritis was associated with increased expression of VCAM‐1, independent of diet. VCAM‐1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM‐1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large‐vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA.

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Section: Discussionsupporting

confidence: 50%

Aortic VCAM‐1: an early marker of vascular inflammation in collagen‐induced arthritis

Denys

Clavel

Lemeiter

et al. 2016

J Cellular Molecular Medi

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“…For example, transgenic LDL-R knockout mice defective in the expression of normal VCAM-1 had reduced susceptibility the atherogenesis (23). Dietary SPI/IF significantly decreased serum VCAM-1 levels in a long term study of surgically post-menopausal female macaques (8), and in post-menopausal women in a genotype dependent manner (24), but not in two short term dietary studies of 6 weeks (25) and 20 weeks (26) duration.…”

Section: Discussionmentioning

confidence: 99%

Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys

Walker¹,

Adams²,

Franke³

et al. 2008

Atherosclerosis

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Male cynomolgus macaques (n=91) consumed an isoflavone (IF)-free, atherogenic control diet containing casein/lactalbumin for five months, then were randomized to three groups: Control (n=30) continued on the control diet; Low IF (n=30) received a mixture of unmodified and IF-depleted soy protein isolate (SPI) (0.94 mg IF/g protein, approximating a human intake of 75 mg/day); and High IF (n=31) received unmodified SPI (1.88 mg IF/g protein, approximating a human intake of 150mg/ day) for 31 months. Iliac and carotid artery atherosclerosis, and arterial and hepatic mRNA transcripts related to inflammation and estrogen receptors (ER) were measured. Trend analysis identified a significant inverse relationship between dietary IF content and plaque area in the iliac (p<0.05) but not carotid arteries (p>0.13). No significant effect of diet on inflammatory gene or estrogen receptor expression was observed. Plaque area was positively correlated with the mRNA transcript levels for arterial MCP-1, ICAM-1, and the macrophage marker CD68 (all r>0.25, p<0.03), and negatively correlated with Erα and ERβ (all r<−0.23, p<0.03). Coronary artery plaque area appeared to be more closely associated with gene expression patterns of the iliac arteries than the carotid arteries. The data suggests benefits of dietary soy on atherosclerotic plaque development in males may be mediated through inflammation-independent pathways. The negative associations of arterial ERα expression with atherosclerosis lend support to a mechanistic role for estrogen receptors in atherosclerosis susceptibility which merits further study.

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“…The study in this issue of the JCI shows, for the first time, that VCAM-1 is critical for the development of atherosclerotic lesions in this LDL receptor knockout mouse model (16). This is important because the LDL receptor knockout mouse is a good model of human atherosclerosis and develops significant lesions when fed a proatherogenic diet.…”

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confidence: 89%