A clinical perspective on the utility of alpha 1 antichymotrypsin for the early diagnosis of calcific aortic stenosis

Martín-Rojas, Tatiana; Mouriño-Álvarez, Laura; Gil-Dones, Félix; Cuesta, Fernando de la; Roselló‐Lletí, Esther; Laborde, Carlos M.; Rivera, Miguel; López-Álmodovar, Luis F.; López, Juan Antonio; Åkerström, Finn; Padial, Luis Rodrı́guez; Barderas, María G.

doi:10.1186/s12014-017-9147-z

Cited by 16 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 Increased plasma SERPINA3 concentrations appeared also predictive of adverse outcome in patients with acute myocardial infarction 26 or associated with calcific aortic stenosis. 27 Our study expands these observations by providing the first direct evidence associating SERPINA3 levels with poor clinical outcome in heart failure. In two distinct cohorts of patients, SERPINA3 levels were consistently higher in non-surviving patients with CCMP or all comers with a de novo or worsened heart failure regardless its phenotype.…”

Section: Serpina3 In Hf Patientssupporting

confidence: 69%

See 1 more Smart Citation

Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure

et al. 2021

View full text Add to dashboard Cite

AimsWe investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and resultsIn the first stage, 83 HF-related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age-matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up-regulated in non-survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P < 0.01 and 334.7 ± 138.7 vs. 228.2 ± 83.1 μg/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 μg/mL were associated with increased all-cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5-3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2-3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N-terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all-cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. ConclusionIn patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.

show abstract

Section: Serpina3 In Hf Patientssupporting

confidence: 69%

“… 9 Increased plasma SERPINA3 concentrations appeared also predictive of adverse outcome in patients with acute myocardial infarction 26 or associated with calcific aortic stenosis. 27 …”

Section: Discussionmentioning

confidence: 99%

Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure

et al. 2021

View full text Add to dashboard Cite

show abstract

“…An increase in alpha-1-antichymotrypsin occurs during tissue damage and it is considered to be one of the “acute phase reactant” [ 115 ]. Moreover, it contributes to the impairment of the coagulation cascade and fibrinolysis in the development of calcific aortic stenosis and could be useful as a biomarker for this disease with considerable clinical value [ 116 ].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

et al. 2021

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs.

show abstract

“…Following our previously published protocol [ 34 , 35 ], samples were reduced with 100 nM DTT in 50 mM ammonium bicarbonate (99% purity; Scharlau, Barcelona, Spain) for 30 min at 37 °C and alkylated with 550 mM iodoacetate in 50 mM ammonium bicarbonate for 20 min at room temperature. Proteins were digested in 50 mM ammonium bicarbonate, 15% acetonitrile (LC-MS grade; Scharlau, Barcelona, Spain) with sequencing-grade modified porcine trypsin (Promega, Madison, WI, USA) at a final concentration of 1:50.…”

Section: Methodsmentioning

confidence: 99%

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis

Martín-Rojas

Sastre-Oliva

Esclarín-Ruz

et al. 2020

JPM

Self Cite

View full text Add to dashboard Cite

Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.

show abstract

A clinical perspective on the utility of alpha 1 antichymotrypsin for the early diagnosis of calcific aortic stenosis

Cited by 16 publications

References 30 publications

Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure

Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure

Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis

Contact Info

Product

Resources

About