S-EPMC9064511 - Associations between Circulating VEGFR2<sup>hi</sup>-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease. - OmicsDI

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Dataset Information

Associations between Circulating VEGFR2^hi-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease.

ABSTRACT:

Background

Neutrophils expressing vascular endothelial growth factor receptor (VEGFR) represent a distinct subtype of neutrophils with proangiogenic properties. The purpose of this study was to identify the interrelations between circulating CD16^hiCD11b^hiCD62L^loCXCR2^hiVEGFR2^hi-neutrophils and indicators of carotid plaque burden in patients without atherosclerotic cardiovascular diseases (ASCVD).

Methods

The study included 145 patients, 51.7% men and 48.3% women, median age-49.0 years. All patients underwent carotid duplex ultrasound scanning. The maximal carotid plaque thickness was used as an indicator of carotid plaque burden. Also, carotid intima-media thickness (cIMT) and femoral IMT were measured. The phenotyping of neutrophil subpopulations was executed by the flow cytometry via the Navios 6/2. Results. The subpopulation of VEGFR2^hi-neutrophils accounted for about 5% of the total pool of circulating neutrophils. A decrease in VEGFR2^hi-neutrophils with an increase in carotid plaque burden was statistically significant (p = 0.036). A decrease in VEGFR2^hi-neutrophils < 4.52% allowed to predict the presence of plaque with a maximum height > 2.1 mm (Q4), with sensitivity of 78.9% and specificity of 61.5% (AUC 0.693; 95% CI 0.575-0.811; p = 0.007). Inverse correlations were established between the carotid and femoral IMT and the absolute and relative number of VEGFR2^hi-neutrophils (p < 0.01).

Conclusion

In patients aged 40-64 years without established ASCVD, with an increase in indicators of the carotid plaque burden, a significant decrease in the proportion of circulating VEGFR2^hi-neutrophils was noticed. A decrease in the relative number of VEGFR2^hi-neutrophils of less than 4.52% made it possible to predict the presence of extent carotid atherosclerosis with sensitivity of 78.9% and specificity of 61.5%.

SUBMITTER: Genkel V

PROVIDER: S-EPMC9064511 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Associations between Circulating VEGFR2<sup>hi</sup>-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease.

Genkel Vadim V Dolgushin Ilya I Baturina Irina I Savochkina Albina A Nikushkina Karina K Minasova Anna A Kuznetsova Alla A Kuznetsova Alla A Shaposhnik Igor I

Journal of immunology research 20220426

<h4>Background</h4>Neutrophils expressing vascular endothelial growth factor receptor (VEGFR) represent a distinct subtype of neutrophils with proangiogenic properties. The purpose of this study was to identify the interrelations between circulating CD16<sup>hi</sup>CD11b<sup>hi</sup>CD62L<sup>lo</sup>CXCR2<sup>hi</sup>VEGFR2<sup>hi</sup>-neutrophils and indicators of carotid plaque burden in patients without atherosclerotic cardiovascular diseases (ASCVD).<h4>Methods</h4>The study included 145 ...[more]

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Project description:ObjectiveCarotid endarterectomy for symptomatic carotid stenosis is recommended for patients with >70% stenosis, but not in those with <50%. Because non-significant, low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by assessing biological features of plaque instability. To challenge risk-stratification based on luminal narrowing, we compared biological features of carotid plaques from symptomatic patients with low-degree (<50%) vs high-degree (>70%) stenosis and explored potential mechanisms behind plaque instability in low-degree stenoses.MethodsEndarterectomy specimens were taken from symptomatic patients with high-degree (n = 204) and low-degree (n = 34) stenosis, all part of the Biobank of Karolinska Endarterectomies. Patient demographics, image-derived plaque morphology, and gene expression analyses of extracted lesions were used for comparisons. Plaque biology was assessed by transcriptomics using dimensionality reduction, differential gene expression, and gene-set enrichment analyses. Immunohistochemistry was used to study proteins corresponding to upregulated genes.ResultsThe demographics of the two groups were statistically similar. Calcification, lipid-rich necrotic core, intraplaque hemorrhage, plaque burden, and fibrous cap thickness were similar in both groups, whereas the sum of lipid-rich necrotic core and intraplaque hemorrhage was higher (P = .033) in the high-degree stenosis group. Dimensionality reduction analysis indicated poor clustering separation of plaque gene expression in low-compared with high-degree stenosis lesions, whereas differential gene expression showed upregulation of hypoxia-inducible factor 3A (log2 fold change, 0.7212; P = .0003), and gene-set enrichment analyses identified pathways related to tissue hypoxia and angiogenesis in low-degree stenoses. Hypoxia-inducible factor 3-alpha protein was associated with smooth muscle cells in neo-vascularized plaque regions.ConclusionsPlaques from symptomatic patients with non-significant low-degree carotid stenoses showed morphologic and biological features of atherosclerotic plaque instability that were comparable to plaques from patients with high-degree stenoses, emphasizing the need for improved stroke risk stratification for intervention in all patients with symptomatic carotid stenosis irrespective of luminal narrowing. An increased expression of hypoxia-inducible factor 3A in low-degree stenotic lesions suggested mechanisms of plaque instability associated with tissue hypoxia and plaque angiogenesis, but the exact role of hypoxia-inducible factor 3A in this process remains to be determined.Clinical relevanceCarotid plaques from symptomatic patients with <50% stenosis show morphologic and biological features of plaque instability, comparable to high-degree stenosis, which emphasizes the need for improved stroke risk stratification beyond stenosis severity.