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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

IPA of a subset of 31 proteins identified in the secretome of RCA specimens. Pathways were generated based on the information stored in IPA Knowledge base. Nodes correspond to the 31 proteins and are reported with their Gene Codes. Extracellular space, cytoplasm, and plasma membrane proteins are shown based on IPA classification. Relationships with disease and cellular functions are evidenced. The relationships that are predicted to lead to activation and to inhibition and those not predicted are reported in orange, blue, and grey, respectively.
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fig3: IPA of a subset of 31 proteins identified in the secretome of RCA specimens. Pathways were generated based on the information stored in IPA Knowledge base. Nodes correspond to the 31 proteins and are reported with their Gene Codes. Extracellular space, cytoplasm, and plasma membrane proteins are shown based on IPA classification. Relationships with disease and cellular functions are evidenced. The relationships that are predicted to lead to activation and to inhibition and those not predicted are reported in orange, blue, and grey, respectively.

Mentions: IPA was used to highlight pathways and diseases which involve secreted proteins. The most represented pathways were those related to cell proliferation, migration, and VSMC activation. Among the proteins that are implicated in atherogenesis and vascular diseases, CHI3L1 was the only one that is predicted as linked to all pathways (Figure 3).


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)

IPA of a subset of 31 proteins identified in the secretome of RCA specimens. Pathways were generated based on the information stored in IPA Knowledge base. Nodes correspond to the 31 proteins and are reported with their Gene Codes. Extracellular space, cytoplasm, and plasma membrane proteins are shown based on IPA classification. Relationships with disease and cellular functions are evidenced. The relationships that are predicted to lead to activation and to inhibition and those not predicted are reported in orange, blue, and grey, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4561865&req=5

fig3: IPA of a subset of 31 proteins identified in the secretome of RCA specimens. Pathways were generated based on the information stored in IPA Knowledge base. Nodes correspond to the 31 proteins and are reported with their Gene Codes. Extracellular space, cytoplasm, and plasma membrane proteins are shown based on IPA classification. Relationships with disease and cellular functions are evidenced. The relationships that are predicted to lead to activation and to inhibition and those not predicted are reported in orange, blue, and grey, respectively.
Mentions: IPA was used to highlight pathways and diseases which involve secreted proteins. The most represented pathways were those related to cell proliferation, migration, and VSMC activation. Among the proteins that are implicated in atherogenesis and vascular diseases, CHI3L1 was the only one that is predicted as linked to all pathways (Figure 3).

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