Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction (from the VCU-Alpha 1-RT Pilot Study)

Abbate, Antonio; Tassell, Benjamín W. Van; Christopher, Sanah; Abouzaki, Nayef; Sonnino, Chiara; Oddi, Claudia; Carbone, Salvatore; Melchior, Ryan; Gambill, Michael Lucas; Roberts, Charlotte; Kontos, Michael C.; Peberdy, Mary Ann; Toldo, Stefano; Vetrovec, George W.; Biondi‐Zoccai, Giuseppe; Dinarello, Charles A.

doi:10.1016/j.amjcard.2014.09.043

Cited by 49 publications

(48 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The loss of statistical significance of sST2 with the addition of the cardiac‐specific biomarker, NT‐proBNP, in the CHS cohort, compared to the retention of ST2 in multiple biomarker statistical models in the FHS cohort, might be explained by differences in the age distributions of the 2 cohorts. Whereas the CHS cohort had a much higher incidence of HF than the younger FHS participants, the lack of cardiac specificity of sST2 potentially limits its cardiovascular prognostic power given the increased prevalence of noncardiovascular inflammatory diseases that mediate sST2 levels in older participants 41. Further evidence also suggesting a lack of cardiac specificity of sST2 in middle‐age adults was found on a subsequent analysis of the FHS cohort for structural heart disease, which found that sST2 levels did not discriminate between individuals with or without left ventricular hypertrophy (LVH) and depressed left ventricular systolic function 42.…”

Section: Discussionmentioning

confidence: 99%

Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community‐Dwelling Population

Parikh

Seliger

Christenson

et al. 2016

JAHA

View full text Add to dashboard Cite

BackgroundSoluble ST2 (sST2), a marker of myocyte stretch and fibrosis, has prognostic value in many cardiovascular diseases. We hypothesized that sST2 levels are associated with incident heart failure (HF), including subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fraction, and cardiovascular death.Methods and ResultsBaseline serum sST2 was measured in 3915 older, community‐dwelling subjects from the Cardiovascular Health Study without prevalent HF. sST2 levels were associated with older age, male sex, black race, traditional cardiovascular risk factors, other biomarkers of inflammation, cardiac stretch, myocardial injury, and fibrosis, and abnormal echocardiographic parameters. In longitudinal analysis, greater sST2 was associated with a higher risk of incident HF and cardiovascular death; however, in multivariate models adjusting for other cardiac risk factors and the cardiac‐specific biomarker, N‐terminal pro–type B natriuretic peptide, these associations were attenuated. In these models, an sST2 level above the US Food and Drug Administration–approved cut‐off value (>35 ng/mL) was significantly associated with incident HF (hazard ratio [HR], 1.20; 95% CI, 1.02–1.43) and cardiovascular death (HR, 1.21; 95% CI, 1.02–1.44), and greater sST2 was continuously associated with cardiovascular death (per 1‐ln increment: HR, 1.24; 95% CI, 1.02–1.50). sST2 was not associated with the HF subtypes of HFpEF and HFrEF in adjusted analysis. Addition of sST2 to existing risk models of HF and cardiovascular death modestly improved discrimination and reclassification into a higher risk.ConclusionsThe predictive value of sST2 for HF of all subtypes and cardiovascular death is modest in an elderly population despite strong cross‐sectional associations with risk factors and underlying cardiac pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community‐Dwelling Population

Parikh

Seliger

Christenson

et al. 2016

JAHA

View full text Add to dashboard Cite

show abstract

“…Although A1AT is commonly used to treat patients with inherited Z (Glu342Lys) deficiency, A1AT has been administered to non-deficient patients with recent onset Type 1 diabetes (22) and ST-elevated myocardial infarction (23). Those studies revealed a distinct anti-inflammatory profile of reduced IL‐1β and C-reactive protein levels.…”

Section: Introductionmentioning

confidence: 99%

α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression

Frenzel

Wrenger

Brügger

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

α1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its anti-protease activity. Here we demonstrate that A1AT (Prolastin®), a potent inducer of Angptl4, contains significant quantities of the fatty acids (FA): linoleic (LA, C18:2) and oleic (OA, C18:1). However, only trace amounts of FAs were present in preparations that failed to increase Angplt4 expression, for example A1AT (Zemaira) or M-type A1AT purified by affinity chromatography. FA pull-down assays with western blot analysis revealed a FA-binding ability of A1AT. In human blood adherent monocytes A1AT‐FA conjugates up-regulated expression of Angptl4 (54.9-fold, p<0.001), fatty acid binding protein 4 (FABP4) (11.4-fold, p<0.001) and to a lesser degree, fatty acid translocase (CD36) (3.1-fold, p<0.001) relative to A1AT devoid of FA (A1AT‐0). These latter effects of A1AT-FA were blocked by inhibitors of PPARβ/δ (ST247) and PPARγ (GW9662). When compared to controls, cell pre-treatment with ST247 diminished the effect of A1AT-LA on Angptl4 mRNA (11.6- vs 4.1-fold, p<0.001) and FABP4 mRNA (5.4-vs 2.8-fold, p<0.001). Similarly, pre-incubation of cells with GW9662 inhibited inducing effect of A1AT-LA on Angptl4 mRNA (by 2-fold, p<0.001) and FABP4 mRNA (by 3-fold, p<0.001). Thus, A1AT binds to FA, and it is this form of A1AT that induces Angptl4 and FABP4 expression via a PPARs-dependent pathway. These findings provide a mechanism for the unexplored area of A1AT biology independent of its anti-protease properties.

show abstract

“…A previous study was unable to detect IL-33 in PsA patients, however, the case number was small (n = 7)17. It is possible that IL-33 may have formed immune complexes with sST2 or is downregulated by sST2 through negative regulatory mechanisms; however, this hypothesis remains unproven until a validated method for sST2-IL-33 complex assay is available18. Nevertheless, the low detection rate could mask the direct correlation between IL-33 and atherosclerosis or compromised bone quality, and limit the utility of blood IL-33 as a biomarker in PsA.…”

Section: Discussionmentioning

confidence: 93%

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Shen

Shang

Wong

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients’ group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53.0 ± 10.1 years). Plasma sST2 levels were significantly higher in 33 (41%) patients with carotid plaques (11.2 ± 4.5 vs 7.7 ± 3.7 ng/ml, P < 0.001). In multivariate analysis, sST2 was an independent explanatory variable associated with carotid plaques (OR = 1.296, 95% CI: [1.091,1.540]; P = 0.003). After adjustment for the osteoporotic risk factors, sST2 was significantly associated with higher cortical porosity (β = 0.184, [0.042,0.325]; P = 0.012) and cortical pore volume (2.247, [0.434,4.060]; P = 0.016); and had a trend to be associated with lower cortical vBMD (−2.918, [−6.111,0.275]; P = 0.073). IL-33 was not associated with carotid plaque or vBMD/microstructure. In conclusion, plasma sST2 levels were independently correlated with both carotid plaque and compromised cortical vBMD/microstructure in PsA patients. IL-33/ST2 axis may be a link between accelerated atherosclerosis and osteoporosis in PsA.

show abstract

Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction (from the VCU-Alpha 1-RT Pilot Study)

Cited by 49 publications

References 12 publications

Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community‐Dwelling Population

Soluble ST2 for Prediction of Heart Failure and Cardiovascular Death in an Elderly, Community‐Dwelling Population

α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2

Contact Info

Product

Resources

About