Cardiovascular Risk and Serum Hyaluronic Acid: A Preliminary Study in a Healthy Population of Low/Intermediate Risk

Papanastasopoulou, Chrysanthi; Papastamataki, Maria; Karampatsis, Petros; Anagnostopoulou, Eleni; Papassotiriou, Ioannis; Sitaras, Nikolaos M.

doi:10.1002/jcla.22010

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…A significant positive correlation was found between HA levels and glycemia in our study population. Our findings were in line with previous studies, also reporting a critical role for HA in DM-related atherosclerosis ( 26 – 29 , 65 ). In vascular dysfunction, HA triggers smooth muscle cells’ dedifferentiation, which contributes to vessel wall thickening.…”

Section: Discussionsupporting

confidence: 94%

“…Hyaluronan (HA) is present in low amount in normal blood vessels but increases in vascular diseases as well as in DM ( 25 ). It seems to have an important role in diabetic angiopathy ( 26 – 28 ) and is associated with an increased risk for developing CAD also in non-diabetic patients ( 29 ). HA is increased in vascular plaques, and its high metabolism causes their destabilization ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

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In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes

et al. 2017

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AimThe leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (DM) is coronary artery disease (CAD), a condition often asymptomatic but severe in these patients. Although glucose metabolism impairment and oxidative stress are known actors in the endothelial dysfunction/remodeling that occurs in diabetic patients, the relationship between cardiovascular disorders and DM is not fully understood. We have performed both an in vivo imaging and in vitro molecular analysis to investigate diabetic-specific CAD alterations.MethodsComputed tomography coronary angiography (CTCA) was performed in a group of 20 diabetic patients with CAD (DM+CAD+), 20 non-diabetic with CAD (DM−CAD+), 10 diabetic non-CAD patients (DM+CAD−), and 20 non-diabetic healthy subjects (HS). Imaging quantitative parameters such as calcium score (Cascore), calcified plaque volume (CPV), non-calcified plaque volume (NCPV), total plaque volume (TPV), remodeling index (RI), and plaque burden were extracted for each CAD subject. Moreover, the expression levels of superoxide dismutase 2 (SOD2) and liver X receptor alpha (LXRα) genes were analyzed in the peripheral blood mononuclear cells, whereas hyaluronan (HA) concentrations were evaluated in the plasma of each subject.ResultsImaging parameters, such as Cascore, CPV, RI, and plaque burden, were significantly higher in DM+CAD+ group, compared to DM−CAD+ (P = 0.019; P = 0.014; P < 0.001, P < 0.001, respectively). SOD2 mRNA was downregulated, while LXRα gene expression was upregulated in DM+CAD−, DM+CAD+, and DM−CAD+ groups compared to HS (P = 0.001, P = 0.03, and P = 0.001 for SOD2 and P = 0.006, P = 0.008, and P < 0.001 for LXRα, respectively). Plasmatic levels of HA were higher in DM−CAD+, DM+CAD−, and DM+CAD+ groups, compared to HS (P = 0.001 for the three groups). When compared to DM−CAD+, HA concentration was higher in DM+CAD− (P = 0.008) and DM+CAD+ (P < 0.001) with a significant difference between the two diabetic groups (P = 0.003). Moreover, HA showed a significant association with diabetes (P = 0.01) in the study population, and the correlation between HA levels and glycemia was statistically significant (ρ = 0.73, P < 0.001).ConclusionIn our population, imaging parameters highlight a greater severity of CAD in diabetic patients. Among molecular parameters, HA is modulated by diabetic CAD-related alterations while SOD2 and LXRα are found to be more associated with CAD but do not discriminate between diabetic and non-diabetic subgroups.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes

et al. 2017

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“…In the present study, we provide evidence that serum levels of HA at stable state were significantly associated with time to death independently of adjusted Charlson score, annual exacerbation rate and BODE index components. It has been shown that HA serum levels are elevated in patients with dyslipidaemia and high cardiovascular risk [26]. In our study, patients included in the validation cohort had numerous comorbidities, including arterial hypertension and coronary arterial disease.…”

Section: Discussionmentioning

confidence: 91%

Serum levels of hyaluronic acid are associated with COPD severity and predict survival

et al. 2019

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“…Additionally, in vitro data suggests that CXCL4 may interact with gp120 to prevent HIV-1 infection of CD4 + T lymphocytes [ 19 , 20 ]. HA is an extracellular matrix component produced during wound healing, and circulating concentrations are increased in fibrotic diseases [ 13 , 21 – 23 ]. In HIV infection, HA has been associated with a 4.6-fold increased risk of death or AIDS diagnosis, and an 8.7-fold increased risk of immune reconstitution inflammatory syndrome within twelve months of ART initiation [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men

et al. 2018

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IntroductionLymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants.MethodsHIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA.ResultsMedian pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01).ConclusionsHigher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.

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Cardiovascular Risk and Serum Hyaluronic Acid: A Preliminary Study in a Healthy Population of Low/Intermediate Risk

Abstract: Serum HA should be explored as an early marker of atheromatosis and cardiovascular risk.

Cited by 15 publications

References 38 publications

In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes

In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes

Serum levels of hyaluronic acid are associated with COPD severity and predict survival

Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men

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