OBJECTIVE: To review relevant literature regarding the role of metformin in angiogenesis among diabetic patients.
METHODS: The systematic review and meta-analysis conducted from May to September 2022, and comprised search on Medline, ScienceDirect, ProQuest, Web of Science, EBSCOhost and Cochrane Library databases. The studies included were published in the English language and were human studies having angiogenesis endothelial markers as the outcomes of interest among patients of type 2 diabetes mellitus undergoing metformin therapy. Endothelial markers, including vascular endothelial growth factor, von-Willebrand-factor, plasminogen activator inhibitor-1, soluble vascular adhesion molecule- 1, intercellular adhesion molecule-1, soluble endothelialselectin, tissue plasminogen activator, urinary albumin excretion, platelet endothelial cell adhesion molecule-1 and thrombin-activatable fibrinolysis inhibitor, were assessed as angiogenesis outcomes. Data was statistically analysed using Review Manager 5.4.
RESULTS: Of the 413 studies identified, 8(1.9%) were included; 5(62.5%) randomised control trials, 2(25.0%) cross-sectional, and 1(12.5%) cohort studies, with overall 1199 patients. Among the outcomes, von-Willebrandfactor (p=0.01), soluble vascular adhesion molecule-1 (p<0.00001), intercellular adhesion molecule-1 (p=0.0003), soluble endothelial-selectin (p=0.007), and tissue plasminogen activator (p<0.00001) showed significantly lower levels after metformin treatment using the random effect methods.
CONCLUSIONS: Metformin was found to have an additional effect of endothelial function improvement.

BACKGROUND: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation\'s effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted.
OBJECTIVE: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors.
METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias.
RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006).
CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

BACKGROUND: The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients.
METHODS: We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS: In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I2 = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I2 = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I2 = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I2 = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I2 = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin).
CONCLUSIONS: The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662.

A number of studies have examined the impact of curcumin/turmeric on blood pressure and the factors allegedly responsible for hypertension. In this systematic review and meta-analysis, we tried to sum up the existing literature on randomized controlled trials (RCTs) investigating this hypothesis.
Online databases (PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar) were searched from inception up to October 2022. We used the cochrane quality assessment tool to evaluate the risk of bias. Outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), blood levels of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), flow-mediated vasodilation (FMD), and pulse-wave velocity (PWV). Weighted mean differences (WMDs) were derived and reported. In case of significant between-study heterogeneity, subgroup analyses were carried out. Significance level was considered as P-values<0.05.
Finally, 35 RCTs out of 4182 studies were included. Our findings suggested that curcumin/turmeric supplementation significantly improved SBP (WMD: -2.02 mmHg; 95 % CI: -2.85, -1.18), DBP (WMD: -0.82 mmHg; 95 % CI: -1.46, -0.18), VCAM-1 (WMD: -39.19 ng/mL; 95 % CI: -66.15, -12.23), and FMD (WMD: 2.00 %; 95 % CI: 1.07, 2.94). However, it did not significantly change levels of ICAM-1 (WMD: -17.05 ng/ml; 95 % CI: -80.79, 46.70), or PWV (WMD: -79.53 cm/s; 95 % CI: -210.38, 51.33).
It seems that curcumin/turmeric supplementation could be regarded as a complementary method to improve blood pressure and endothelial function. However, further research is needed to clarify its impact on inflammatory adhesion molecules in the circulation.

Aim Although antiretroviral therapy (ART) is available, the rate of new HIV infections is alarming. With this trend, it is anticipated that the use of ART will continue to rise, potentially resulting in associated vascular disorders. Therefore, we aimed to examine the impact of ART on endothelial function in people living with HIV (PLHIV), a predictor of cardiovascular diseases.
A comprehensive search for evidence was made on PubMed and Scopus on May 06, 2023, following the Preferred Reporting Items for Systematic Review and Meta-analysis. Cochrane and Newcastle-Ottawa quality assessment scales were used to evaluate quality, while the metaHun web tool and Review Manager version 5.4.1 were used for analysis. Subgroup, sensitivity, and publication bias were conducted for each outcome measure.
We identified 37 studies, including a sample size of 3700 with 2265 individuals on ART. The analyzed evidence showed a large significant effect of ART on vascular cell adhesion molecule-1, with a standardized mean difference (SMD) of -1.23 (95 % CI: -1.72, -0.74; p = 0.0013). Similarly, a significant medium effect of ART was observed on intercellular cell adhesion molecule-1 in PLHIV, with an SMD of -1.28 (95 % CI: -2.00, -0.56; p = 0.0231) compared to the control group. Furthermore, ART exhibited a significant but small effect on flow-mediated dilation (FMD) with an SMD of -0.40 (95 % CI: -0.62, -0.19, p = 0.0159).
Our findings show an improved endothelial function in PLHIV on ART, as demonstrated by reduced adhesion molecules; however, ART exhibited a small effect on FMD, thus suggesting PLHIV on ART may still be at risk of endothelial dysfunction and further cardiovascular diseases.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

BACKGROUND: Increasing evidence suggests an association between schizophrenia and atherosclerosis. We conducted a systematic review and meta-analysis of cell adhesion molecules, critically involved in early atherosclerosis, in schizophrenia.
METHODS: We searched electronic databases from inception to 11 November 2023 for case-control studies assessing vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, and Down syndrome cell, DSCAM, adhesion molecules, selectins (E-, L-, and P-selectin), integrins, and cadherins in patients with schizophrenia and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively.
RESULTS: In 19 eligible studies, there were non-significant between-group differences in the concentrations of cell adhesion molecules, barring higher P-selectin in patients with schizophrenia (standard mean difference, SMD = 2.05, 95 % CI 0.72 to 3.38, p = 0.003; I2 = 97.2 %, p<0.001; very low certainty of evidence). Limited or no information was available regarding PECAM-1, DSCAM, ESAM, integrins, and cadherins. In meta-regression and subgroup analysis, there were significant associations between the SMD of ICAM-1 and matrix used (plasma or serum) and pharmacological treatment of schizophrenia, and between the SMD of VCAM-1 and pharmacological treatment, but not with other study and patient characteristics.
CONCLUSIONS: The results of our systematic review and meta-analysis do not support a significant role of immunoglobulin-like adhesion molecules, selectins, integrins, or cadherins in mediating the associations between schizophrenia, atherosclerosis, and cardiovascular disease. Further studies are warranted to investigate these associations in patients with different cardiovascular risk and the effects of antipsychotic treatments on cell adhesion molecules and surrogate markers of atherosclerosis (PROSPERO registration number: CRD42023463916).

Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: -1.26, 95% CI: -1.88 to -0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: -1.76, 95%CI: -3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: -0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: -2.67, 95%CI: -5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

The current meta-analysis investigated the effects of exercise training on circulating adhesion molecules i.e. soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in adults.
PubMed, Web of Science, Scopus and Embase were searched to identify original articles, published in English languages journal from inception up to 31 August 2023 that compared the effects of exercise training with non-exercising control on sICAM-1 and sVCAM-1 in adults. Standardized mean differences (SMDs) and 95% CIs were calculated using random-effect models.
Twenty-three studies including 31 intervention arms and involving 1437 subjects were included in the meta-analysis. Exercise training effectively reduced sICAM-1 [SMD: -0.33 (95% CI -0.56 to -0.11), p = 0.004; I2 = 56.38%, p = 0.001; 23 intervention arms]. Subgroup analyses showed that sICAM-1 decreased in adults with age <60 years (p = 0.01) and BMI ≥ 27 kg/m2 (p = 0.002) and those with metabolic disorders (p = 0.004) and cardiovascular diseases (p = 0.005). In addition, aerobic (p = 0.02) and resistance training (p = 0.007) are effective in reducing sICAM-1. However, exercise training did not indicate a superior effect on sVCAM-1 [SMD: -0.12 (95% CI -0.29 to 0.05), p = 0.17; I2 = 36.29%, p = 0.04; 23 intervention arms].
Our results show that exercise training reduces sICAM-1, but not for sVCAM-1, where both aerobic and resistance training is effective in reducing sICAM-1 in adults with metabolic disorders and cardiovascular diseases.
The current meta-analysis was registered at www.crd.york.ac.uk/prospero with ID registration number: CRD42023410474.

Endothelial dysfunction is closely linked to the development of atherosclerosis. This systematic review and meta-analysis reviewed the evidence on the effect of weight loss, achieved by dietary-based interventions, on biomarkers of endothelial function (EF). Two databases (Medline, Embase) were searched from inception until November 2022 for studies that met the following criteria: 1) adult subjects (≥ 18 years) without exclusion for health status, 2) dietary interventions for weight loss, and 3) measurements of changes in EF biomarkers. Random-effect meta-analysis and meta-regression were performed. Thirty-seven articles including 1449 participants were included in the systematic review. Study duration ranged from 3-52 weeks. Overall, weight loss significantly improved biomarkers of EF [standardised mean difference (SMD):0.65; 95%CI:0.49,0.81; P < 0.001;I2 = 91.9%]. Subgroup analyses showed weight loss significantly improved levels of E-selectin (P < 0.001), intercellular adhesion molecule-1 (ICAM-1) (P < 0.001), vascular cell adhesion molecule-1 (VCAM-1) (P < 0.001), nitrite/nitrate (NOx) (P < 0.001) and vascular endothelial growth factor (VEGF) (P < 0.001). Conversely, there was no significant improvement for von Willebrand Factor (vWF). Meta-regression analysis revealed that changes in EF biomarkers were not affected by age, BMI, quality of the studies or the amount of weight lost. A significant heterogeneity was observed for the effects of weight loss on changes in EF biomarkers. Dietary-induced weight loss may be associated with biomarkers changes indicating an improvement of EF, and it may represent a potential strategy to reduce atherosclerotic risk.