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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

Representative photomicrographs of immunostained consecutive cross sections of RCA in a typical ATH case of HF group (immunopositive cells are dark brown). Immunostained sections demonstrate tissue codistribution (top row) and cell colocalization (middle and bottom rows) of anti-CHI3L1 with anti-αSM-actin and with anti-S100A4 antibodies in a fibrolipid plaque. Enlargements of plaque regions (black and red insets) are displayed in middle and bottom row, respectively. Plaque areas labelled by anti-αSM-actin, anti-S100A4, and anti-CHI3L1 antibodies are indicated (top panels, black arrows; bar = 200 μm) and colocalization of all three antibodies in the same cell type evidenced (bottom panels, black arrows; bar = 10 μm). CHI3L1 immunopositive cells resulted also in αSM-actin or S100A4 positive or both (middle panels, red arrows; bar = 20 μm).
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fig5: Representative photomicrographs of immunostained consecutive cross sections of RCA in a typical ATH case of HF group (immunopositive cells are dark brown). Immunostained sections demonstrate tissue codistribution (top row) and cell colocalization (middle and bottom rows) of anti-CHI3L1 with anti-αSM-actin and with anti-S100A4 antibodies in a fibrolipid plaque. Enlargements of plaque regions (black and red insets) are displayed in middle and bottom row, respectively. Plaque areas labelled by anti-αSM-actin, anti-S100A4, and anti-CHI3L1 antibodies are indicated (top panels, black arrows; bar = 200 μm) and colocalization of all three antibodies in the same cell type evidenced (bottom panels, black arrows; bar = 10 μm). CHI3L1 immunopositive cells resulted also in αSM-actin or S100A4 positive or both (middle panels, red arrows; bar = 20 μm).

Mentions: Anti-CHI3L1, anti-αSM-actin, and anti-S100A4 antibodies labelled the same region in all lesion types observed in adjacent consecutive HF RCA sections, demonstrating a consistent tissue codistribution. Colocalization of the three antibodies in the same cell type was also observed in several microscopic fields of HF RCA ATH cases (Figure 5).


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)

Representative photomicrographs of immunostained consecutive cross sections of RCA in a typical ATH case of HF group (immunopositive cells are dark brown). Immunostained sections demonstrate tissue codistribution (top row) and cell colocalization (middle and bottom rows) of anti-CHI3L1 with anti-αSM-actin and with anti-S100A4 antibodies in a fibrolipid plaque. Enlargements of plaque regions (black and red insets) are displayed in middle and bottom row, respectively. Plaque areas labelled by anti-αSM-actin, anti-S100A4, and anti-CHI3L1 antibodies are indicated (top panels, black arrows; bar = 200 μm) and colocalization of all three antibodies in the same cell type evidenced (bottom panels, black arrows; bar = 10 μm). CHI3L1 immunopositive cells resulted also in αSM-actin or S100A4 positive or both (middle panels, red arrows; bar = 20 μm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Representative photomicrographs of immunostained consecutive cross sections of RCA in a typical ATH case of HF group (immunopositive cells are dark brown). Immunostained sections demonstrate tissue codistribution (top row) and cell colocalization (middle and bottom rows) of anti-CHI3L1 with anti-αSM-actin and with anti-S100A4 antibodies in a fibrolipid plaque. Enlargements of plaque regions (black and red insets) are displayed in middle and bottom row, respectively. Plaque areas labelled by anti-αSM-actin, anti-S100A4, and anti-CHI3L1 antibodies are indicated (top panels, black arrows; bar = 200 μm) and colocalization of all three antibodies in the same cell type evidenced (bottom panels, black arrows; bar = 10 μm). CHI3L1 immunopositive cells resulted also in αSM-actin or S100A4 positive or both (middle panels, red arrows; bar = 20 μm).
Mentions: Anti-CHI3L1, anti-αSM-actin, and anti-S100A4 antibodies labelled the same region in all lesion types observed in adjacent consecutive HF RCA sections, demonstrating a consistent tissue codistribution. Colocalization of the three antibodies in the same cell type was also observed in several microscopic fields of HF RCA ATH cases (Figure 5).

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