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Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine.

Rocchiccioli S, Cecchettini A, Ucciferri N, Terreni M, Viglione F, Trivella MG, Citti L, Parodi O, Pelosi G - Dis. Markers (2015)

Bottom Line: In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent.Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression.A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases.

View Article: PubMed Central - PubMed

Affiliation: National Research Council, Institute of Clinical Physiology, Via Moruzzi, 56124 Pisa, Italy.

ABSTRACT
A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.

No MeSH data available.


Related in: MedlinePlus

Pie charts of the total identified proteins from CTRL and HF. (a) Identified proteins are classified, based on Gene Ontology, according to their localization in intracellular or extracellular space. (b) Identified proteins are evaluated with SecretomeP software to compute their secretion potential. They were divided into classically secreted, not classically secreted, and not predicted.
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fig2: Pie charts of the total identified proteins from CTRL and HF. (a) Identified proteins are classified, based on Gene Ontology, according to their localization in intracellular or extracellular space. (b) Identified proteins are evaluated with SecretomeP software to compute their secretion potential. They were divided into classically secreted, not classically secreted, and not predicted.

Mentions: 224 proteins were identified across all samples with a Protein Score (Confidence) > 95% and local false discovery rate analysis < 1% as stringent criterion to avoid false positives (Table S1 in Supplemtary Material). Proteins were grouped using Gene Ontology (http://www.geneontology.org) and divided in exocytosis pathway related, cell membrane and associated, cytoskeleton and associated, intracellular, and ECM associated proteins (Figure 2(a)). The secretion potential of identified proteins was computed by submitting them to SecretomeP tool which uses specific databases to predict a classical secretion via endoplasmic reticulum (presence of signal peptide) or not classical secretion through the multivesicular bodies [23] (Figure 2(b)).


Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine.

Rocchiccioli S, Cecchettini A, Ucciferri N, Terreni M, Viglione F, Trivella MG, Citti L, Parodi O, Pelosi G - Dis. Markers (2015)

Pie charts of the total identified proteins from CTRL and HF. (a) Identified proteins are classified, based on Gene Ontology, according to their localization in intracellular or extracellular space. (b) Identified proteins are evaluated with SecretomeP software to compute their secretion potential. They were divided into classically secreted, not classically secreted, and not predicted.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4561865&req=5

fig2: Pie charts of the total identified proteins from CTRL and HF. (a) Identified proteins are classified, based on Gene Ontology, according to their localization in intracellular or extracellular space. (b) Identified proteins are evaluated with SecretomeP software to compute their secretion potential. They were divided into classically secreted, not classically secreted, and not predicted.
Mentions: 224 proteins were identified across all samples with a Protein Score (Confidence) > 95% and local false discovery rate analysis < 1% as stringent criterion to avoid false positives (Table S1 in Supplemtary Material). Proteins were grouped using Gene Ontology (http://www.geneontology.org) and divided in exocytosis pathway related, cell membrane and associated, cytoskeleton and associated, intracellular, and ECM associated proteins (Figure 2(a)). The secretion potential of identified proteins was computed by submitting them to SecretomeP tool which uses specific databases to predict a classical secretion via endoplasmic reticulum (presence of signal peptide) or not classical secretion through the multivesicular bodies [23] (Figure 2(b)).

Bottom Line: In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent.Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression.A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases.

View Article: PubMed Central - PubMed

Affiliation: National Research Council, Institute of Clinical Physiology, Via Moruzzi, 56124 Pisa, Italy.

ABSTRACT
A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.

No MeSH data available.


Related in: MedlinePlus