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Immune modulation of vascular resident cells by Axl orchestrates carotid intima-media thickening.

ABSTRACT: Cellular mechanisms of carotid intima-media thickening (IMT) are largely unknown. The receptor tyrosine kinase Axl is essential for function of both bone marrow (BM) and non-BM cells. We studied the mechanisms by which Axl expression in BM-derived cells (compared with non-BM-derived cells) mediates carotid IMT. Partial ligation of the left carotid artery resulted in a similar carotid blood flow reduction in Axl chimeras. Neither irradiation nor bone marrow transplantation had any effect on the 40% difference in carotid IMT between Axl genotypes. Axl-dependent survival is very important for intimal leukocytes; however, Axl expression in BM cells contributes to <30% of carotid IMT. Axl in non-BM cells has a greater effect on carotid remodeling. Expression of Axl in non-BM cells is crucial for the up-regulation of several key proinflammatory signals (eg, IL-1) in the carotid. We found that Axl is involved in immune activation of cultured smooth muscle cells and in immune heterogeneity of medial cells (measured by major histocompatibility complex class II) after carotid injury. Finally, a lack of Axl in non-BM cells increased collagen I? expression, which may play a critical role in carotid remodeling. Our data suggest that Axl contributes to carotid remodeling not only by inhibition of apoptosis but also via regulation of immune heterogeneity of vascular cells, cytokine/chemokine expression, and extracellular matrix remodeling.

SUBMITTER: Gerloff J

PROVIDER: S-EPMC3349833 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other

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Immune modulation of vascular resident cells by Axl orchestrates carotid intima-media thickening.

Gerloff Janice J Korshunov Vyacheslav A VA

The American journal of pathology 20120501 5

Cellular mechanisms of carotid intima-media thickening (IMT) are largely unknown. The receptor tyrosine kinase Axl is essential for function of both bone marrow (BM) and non-BM cells. We studied the mechanisms by which Axl expression in BM-derived cells (compared with non-BM-derived cells) mediates carotid IMT. Partial ligation of the left carotid artery resulted in a similar carotid blood flow reduction in Axl chimeras. Neither irradiation nor bone marrow transplantation had any effect on the 4 ...[more]

PMID: 22538191

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Project description:Background Helicobacter pylori (H. pylori) infection affects ≈4.4 billion people worldwide. Several studies suggest that this pathogen impacts the digestive system, causing diverse and severe conditions, and results in extragastrointestinal disorders like vascular diseases. Our study aims to examine the association between H. pylori infection and carotid intima-media thickness. Methods and Results Electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, and Scopus) were searched for studies, comparing the thickness of the carotid intima-media in H. pylori-infected and noninfected individuals listed until October 20, 2020. Statistical analyses were performed using the random effects meta-analysis of model of weighted mean differences with the corresponding 95% CI using the DerSimonian and Laird method. The protocol was registered in advance in PROSPERO (International Prospective Register of Systematic Reviews; CRD42021224485). Thirteen studies were found meeting inclusion criteria for our systematic review and meta-analysis, presenting data on the thickness of the carotid intima-media considering the presence of H. pylori infection. Altogether, 2298 individuals' data were included (1360 H. pylori positive, 938 negative). The overall carotid intima-media thickness was significantly larger among infected patients compared with uninfected participants (weighted mean difference: 0.07 mm; 95% CI, 0.02-0.12; P=0.004; I2=91.1%; P<0.001). In case of the right common carotid artery, the intima-media thickening was found to be significant as well (weighted mean difference, 0.08 mm; 95% CI, 0.02-0.13, P=0.007; I2=85.1%; P<0.001), while it showed no significance in the left common carotid artery (weighted mean difference, 0.12 mm; 95% CI, -0.05 to 0.28, P=0.176; I2=97.4%; P<0.001). Conclusions H. pylori infection is associated with increased carotid intima-media thickness. Therefore, the infection may indirectly contribute to the development of major vascular events.

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

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Immune modulation of vascular resident cells by Axl orchestrates carotid intima-media thickening.

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Immune modulation of vascular resident cells by Axl orchestrates carotid intima-media thickening.

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