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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

Morphometric results (panel (a)) and histologic characterization (panels (b)–(i)) of arterial segments used for secretome analysis. Panel (a): average values ± SD of intima to media ratio (IMT) at maximal intimal thickening site in CTRL RCA, HF FA, and HF RCA segments used for secretome analysis (n = 6 each). P < 0.05 HF RCA versus all other segments. Panels (b)–(i): representative photomicrographs of H&E and Masson's trichrome stained longitudinal sections of arterial segments: intact (b) or initial type I thickening (c) in typical CTRL RCA and HF FA segments, respectively; HF RCA segments showed preatherosclerotic lesions (HF RCA pre-ATH) classifiable as Stary type I lesion (d), type II fatty streak (e), and type III lesion (f), or atheromas (black arrows, HF RCA ATH segments) classifiable as type IV ((g) and (h)) and as type V fibroatheroma ((i), fibrous cap: asterisk). Low power micrographs, bar = 500 μm, high power insets, bar = 50 μm. I = intima, M = media, A = adventitia.
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fig1: Morphometric results (panel (a)) and histologic characterization (panels (b)–(i)) of arterial segments used for secretome analysis. Panel (a): average values ± SD of intima to media ratio (IMT) at maximal intimal thickening site in CTRL RCA, HF FA, and HF RCA segments used for secretome analysis (n = 6 each). P < 0.05 HF RCA versus all other segments. Panels (b)–(i): representative photomicrographs of H&E and Masson's trichrome stained longitudinal sections of arterial segments: intact (b) or initial type I thickening (c) in typical CTRL RCA and HF FA segments, respectively; HF RCA segments showed preatherosclerotic lesions (HF RCA pre-ATH) classifiable as Stary type I lesion (d), type II fatty streak (e), and type III lesion (f), or atheromas (black arrows, HF RCA ATH segments) classifiable as type IV ((g) and (h)) and as type V fibroatheroma ((i), fibrous cap: asterisk). Low power micrographs, bar = 500 μm, high power insets, bar = 50 μm. I = intima, M = media, A = adventitia.

Mentions: Histologic features and average values of IMT ratio of the segments processed for secretome analysis are shown in Figure 1.


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)

Morphometric results (panel (a)) and histologic characterization (panels (b)–(i)) of arterial segments used for secretome analysis. Panel (a): average values ± SD of intima to media ratio (IMT) at maximal intimal thickening site in CTRL RCA, HF FA, and HF RCA segments used for secretome analysis (n = 6 each). P < 0.05 HF RCA versus all other segments. Panels (b)–(i): representative photomicrographs of H&E and Masson's trichrome stained longitudinal sections of arterial segments: intact (b) or initial type I thickening (c) in typical CTRL RCA and HF FA segments, respectively; HF RCA segments showed preatherosclerotic lesions (HF RCA pre-ATH) classifiable as Stary type I lesion (d), type II fatty streak (e), and type III lesion (f), or atheromas (black arrows, HF RCA ATH segments) classifiable as type IV ((g) and (h)) and as type V fibroatheroma ((i), fibrous cap: asterisk). Low power micrographs, bar = 500 μm, high power insets, bar = 50 μm. I = intima, M = media, A = adventitia.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Morphometric results (panel (a)) and histologic characterization (panels (b)–(i)) of arterial segments used for secretome analysis. Panel (a): average values ± SD of intima to media ratio (IMT) at maximal intimal thickening site in CTRL RCA, HF FA, and HF RCA segments used for secretome analysis (n = 6 each). P < 0.05 HF RCA versus all other segments. Panels (b)–(i): representative photomicrographs of H&E and Masson's trichrome stained longitudinal sections of arterial segments: intact (b) or initial type I thickening (c) in typical CTRL RCA and HF FA segments, respectively; HF RCA segments showed preatherosclerotic lesions (HF RCA pre-ATH) classifiable as Stary type I lesion (d), type II fatty streak (e), and type III lesion (f), or atheromas (black arrows, HF RCA ATH segments) classifiable as type IV ((g) and (h)) and as type V fibroatheroma ((i), fibrous cap: asterisk). Low power micrographs, bar = 500 μm, high power insets, bar = 50 μm. I = intima, M = media, A = adventitia.
Mentions: Histologic features and average values of IMT ratio of the segments processed for secretome analysis are shown in Figure 1.

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