P-selectin and subclinical and clinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Bielinski, Suzette J.; Berardi, Cecilia; Decker, Paul A.; Kirsch, Phillip S.; Larson, Nicholas B.; Pankow, James S.; Sale, Michèle M.; Andrade, Mariza de; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q.; Wassel, Christina L.; Polak, Joseph F.; Tsai, Michael Y.

doi:10.1016/j.atherosclerosis.2015.02.036

Cited by 55 publications

(43 citation statements)

References 45 publications

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“…In a cross-sectional analysis of the Chennai Urban Rural Epidemiology Study, P-selectin levels were found to be higher in those with prevalent diabetes compared with those with normal or impaired glucose tolerance [26]. Similarly, in an earlier analysis of the MESA cohort, we found that prevalence of diabetes increased from lower to higher categories of P-selectin level, and there was heterogeneity across racial/ ethnic groups in the strength of association between P-selectin and outcomes such as prevalent diabetes and coronary artery calcium [27]. In the Framingham Study, no associations were found between P-selectin and incident diabetes in adjusted models, in accordance with the present results [28].…”

Section: Discussionsupporting

confidence: 66%

Circulating cellular adhesion molecules and risk of diabetes: the Multi‐Ethnic Study of Atherosclerosis (MESA)

et al. 2016

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Aims To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes. Methods Soluble levels of six cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin and P-selectin) were measured in participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study. Participants were then followed for up to 10 years to ascertain incident diabetes. Results Sample sizes ranged from 826 to 2185. After adjusting for age, sex, race/ethnicity, BMI and fasting glucose or HbA1c, four cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1 and E-cadherin) were positively associated with incident diabetes and there was a statistically significant trend across quartiles. Comparing the incidence of diabetes in the highest and lowest quartiles of each cellular adhesion molecule, the magnitude of association was largest for E-selectin (hazard ratio 2.49; 95% CI 1.26–4.93) and ICAM-1 (hazard ratio 1.76; 95% CI 1.22–2.55) in fully adjusted models. Tests of effect modification by racial/ethnic group and sex were not statistically significant for any of the cellular adhesion molecules (P>0.05). Conclusions The finding of significant associations between multiple cellular adhesion molecules and incident diabetes may lend further support to the hypothesis that microvascular endothelial dysfunction contributes to risk of diabetes.

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Section: Discussionsupporting

confidence: 66%

Circulating cellular adhesion molecules and risk of diabetes: the Multi‐Ethnic Study of Atherosclerosis (MESA)

et al. 2016

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“…Hwang et al 14 identified lower circulation of sICAM-1 in African Americans compared to subjects of European ancestry, while significant racial/ethnic differences in sICAM-1 concentrations were similarly observed between Asian, Hispanic, black, and non-Hispanic white subjects in the Women’s Health Study 18 . Racial/ethnic differences have also been observed for sP-selectin 19 , sE-selectin 17, 20 and vWF 21, 22 . Although circulating levels of CAMs are highly heritable 23, 24 , and genetic studies have consistently identified associations between soluble levels and the ABO locus 25-29 , associations between ABO blood type and endothelial markers in diverse populations have not been extensively studied.…”

Section: Introductionmentioning

confidence: 94%

ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis

et al. 2016

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Background and aims ABO blood type is associated with cardiovascular disease, although the underlying mechanisms are presumed to be complex. While the relationship between non-O blood types and von Willebrand Factor (vWF) is well-established, associations with cellular adhesion molecules (CAMs) across diverse populations are understudied. Methods We genetically inferred ABO alleles for N=6202 participants from the Multi-Ethnic Study of Atherosclerosis. Linear regression was used to evaluate associations between major ABO allele dosages and log-transformed measurements of vWF (N=924), soluble E-selectin (sE-selectin, N=925), soluble P-selectin (sP-selectin, N=2392), and soluble ICAM-1 (sICAM-1, N=2236) by race/ethnicity. Results For the selectins, the A1 allele was associated with significantly lower levels for all races/ethnicities, with each additional allele resulting in a 28-39% decrease in sE-selectin and 10-18% decrease in sP-selectin relative to Type O subjects. However, the A2 allele demonstrated effect heterogeneity across race/ethnicity for sE-selectin, with lower levels for non-Hispanic whites (p=0.0011) but higher levels for Hispanics (p=0.0021). We also identified elevated sP-selectin levels for B-allele carriers solely in Hispanic participants (p=1.0E-04). ABO-by-race/ethnicity interactions were significant for both selectins (p <0.0125). More modest associations were observed between A1 allele dosage and levels of sICAM-1, with ABO alleles explaining 0.8-1.1% of the total phenotypic variation within race/ethnicity. ABO associations with vWF activity were consistent across race/ethnicity, with B allele carriers corresponding to the highest vWF activity levels. Conclusions ABO blood type demonstrates complex associations with endothelial markers that are largely generalizable across diverse populations.

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“…Stored in the alpha-granules of platelets, in a setting of inflammation P-selectin translocates to the plasma membrane where it can interact with ligands [84] leading to leukocyte-platelet aggregates that promote adhesion and infiltration of inflammatory cells [85][86][87][88]. sP-selectin has been associated with adiposity and both clinical and subclinical atherosclerosis [89] and has been shown to predict atherosclerosis independently of BMI and other CVD risk factors. The enhanced plasma concentrations of P-selectin in overweight and obese insulin resistant subjects [61,90] are reduced after weight loss [61].…”

Section: Soluble P-selectinmentioning

confidence: 99%

Influence of Cardiometabolic Risk Factors on Platelet Function

Barale

Russo

2020

IJMS

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Platelets are key players in the thrombotic processes. The alterations of platelet function due to the occurrence of metabolic disorders contribute to an increased trend to thrombus formation and arterial occlusion, thus playing a major role in the increased risk of atherothrombotic events in patients with cardiometabolic risk factors. Several lines of evidence strongly correlate metabolic disorders such as obesity, a classical condition of insulin resistance, dyslipidemia, and impaired glucose homeostasis with cardiovascular diseases. The presence of these clinical features together with hypertension and disturbed microhemorrheology are responsible for the prothrombotic tendency due, at least partially, to platelet hyperaggregability and hyperactivation. A number of clinical platelet markers are elevated in obese and type 2 diabetes (T2DM) patients, including the mean platelet volume, circulating levels of platelet microparticles, oxidation products, platelet-derived soluble P-selectin and CD40L, thus contributing to an intersection between obesity, inflammation, and thrombosis. In subjects with insulin resistance and T2DM some defects depend on a reduced sensitivity to mediators-such as nitric oxide and prostacyclin-playing a physiological role in the control of platelet aggregability. Furthermore, other alterations occur only in relation to hyperglycemia. In this review, the main cardiometabolic risk factors, all components of metabolic syndrome involved in the prothrombotic tendency, will be taken into account considering some of the mechanisms involved in the alterations of platelet function resulting in platelet hyperactivation.

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P-selectin and subclinical and clinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Cited by 55 publications

References 45 publications

Circulating cellular adhesion molecules and risk of diabetes: the Multi‐Ethnic Study of Atherosclerosis (MESA)

Circulating cellular adhesion molecules and risk of diabetes: the Multi‐Ethnic Study of Atherosclerosis (MESA)

ABO blood group associations with markers of endothelial dysfunction in the Multi-Ethnic Study of Atherosclerosis

Influence of Cardiometabolic Risk Factors on Platelet Function

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