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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

Correlation between secreted and tissue coronary CHI3L1 expression (by LC-MS/MS analysis and immunohistochemistry, resp.) and IMT ratio of corresponding segments at different Stary stages. Representative photomicrographs at low (bar = 200 μm) and high magnification (enlargements of intimal lesion area, insets; bar = 50 μm) from CHI3L1 antibody labeled cross sections of HF RCA segments (from (a) to (f)), according to ATS grade (Stary types I to V) demonstrate the correlation of CHI3L1 expression (dark brown staining indicates positivity) and of ATS stage with secreted CHI3L1 values (arrows). Secreted CHI3L1 expression (blue dots) and CHI3L1 immunoreactivity, expressed as percentage of intralesional positive cell area (red squares), hold direct and significantly linear relations (R2 > 0.8) with the IMT ratio of the same segments.
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fig4: Correlation between secreted and tissue coronary CHI3L1 expression (by LC-MS/MS analysis and immunohistochemistry, resp.) and IMT ratio of corresponding segments at different Stary stages. Representative photomicrographs at low (bar = 200 μm) and high magnification (enlargements of intimal lesion area, insets; bar = 50 μm) from CHI3L1 antibody labeled cross sections of HF RCA segments (from (a) to (f)), according to ATS grade (Stary types I to V) demonstrate the correlation of CHI3L1 expression (dark brown staining indicates positivity) and of ATS stage with secreted CHI3L1 values (arrows). Secreted CHI3L1 expression (blue dots) and CHI3L1 immunoreactivity, expressed as percentage of intralesional positive cell area (red squares), hold direct and significantly linear relations (R2 > 0.8) with the IMT ratio of the same segments.

Mentions: On the basis of these results, anti-CHI3L1 antibody was used to quantify tissue expression of this protein and associate it with localization of other lesional VSMC markers and with ATS grade and morphometric indexes of lesion extent (Figure 4).


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)

Correlation between secreted and tissue coronary CHI3L1 expression (by LC-MS/MS analysis and immunohistochemistry, resp.) and IMT ratio of corresponding segments at different Stary stages. Representative photomicrographs at low (bar = 200 μm) and high magnification (enlargements of intimal lesion area, insets; bar = 50 μm) from CHI3L1 antibody labeled cross sections of HF RCA segments (from (a) to (f)), according to ATS grade (Stary types I to V) demonstrate the correlation of CHI3L1 expression (dark brown staining indicates positivity) and of ATS stage with secreted CHI3L1 values (arrows). Secreted CHI3L1 expression (blue dots) and CHI3L1 immunoreactivity, expressed as percentage of intralesional positive cell area (red squares), hold direct and significantly linear relations (R2 > 0.8) with the IMT ratio of the same segments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Correlation between secreted and tissue coronary CHI3L1 expression (by LC-MS/MS analysis and immunohistochemistry, resp.) and IMT ratio of corresponding segments at different Stary stages. Representative photomicrographs at low (bar = 200 μm) and high magnification (enlargements of intimal lesion area, insets; bar = 50 μm) from CHI3L1 antibody labeled cross sections of HF RCA segments (from (a) to (f)), according to ATS grade (Stary types I to V) demonstrate the correlation of CHI3L1 expression (dark brown staining indicates positivity) and of ATS stage with secreted CHI3L1 values (arrows). Secreted CHI3L1 expression (blue dots) and CHI3L1 immunoreactivity, expressed as percentage of intralesional positive cell area (red squares), hold direct and significantly linear relations (R2 > 0.8) with the IMT ratio of the same segments.
Mentions: On the basis of these results, anti-CHI3L1 antibody was used to quantify tissue expression of this protein and associate it with localization of other lesional VSMC markers and with ATS grade and morphometric indexes of lesion extent (Figure 4).

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