Extracellular Matrix Proteomics in Cardiac Ischemia/Reperfusion

Q: What is the clinical evidence from this study?

Study design: Editorial. Population: Myocardial ischemia and reperfusion (I/R) / ischemic cardiomyopathy. Intervention: Extracellular matrix (ECM) proteomic enrichment and liquid chromatography tandem mass spectrometry (LC-MS) analysis vs. Control animals without ischemia/reperfusion. Primary outcome: Identification of cardiac extracellular matrix (ECM) proteins post-ischemia/reperfusion.

Q: What does this research mean for the field?

Extracellular matrix proteomics identifies dynamic spatial and temporal changes across 139 ECM proteins, including 15 novel cardiac ECM proteins, following cardiac ischemia and reperfusion. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kristine Y. DeLeon‐Pennell; Lisandra E. de Castro Brás; Richard A. Lange; Merry L. Lindsey

doi:10.1161/circulationaha.111.086835

January 19, 2012CirculationOpen Access

Extracellular Matrix Proteomics in Cardiac Ischemia/Reperfusion

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Key result

Extracellular matrix proteomics identified 139 ECM proteins, including 15 novel cardiac ECM proteins, in porcine hearts subjected to 2 hours of ischemia and 15 or 60 days of reperfusion.

Key Points

To characterize qualitative, quantitative, spatial, and temporal alterations in cardiac extracellular matrix proteins following myocardial ischemia and reperfusion.
Porcine hearts subjected to 2 hours of ischemia followed by 15 or 60 days of reperfusion were compared with control animals without ischemia/reperfusion.
Infarcted and border zone left ventricle tissues were enriched for extracellular matrix proteins and evaluated using liquid chromatography tandem mass spectrometry and real-time PCR.
Novel cardiac extracellular matrix proteins identified in the animal model were cross-validated in left ventricular tissue from patients with ischemic cardiomyopathy at the time of transplantation.
Mass spectrometry identified 139 extracellular matrix proteins in porcine hearts, including 15 proteins identified for the first time in cardiac extracellular matrix.
Temporal remodeling demonstrated robust fibronectin expression at day 15 post-reperfusion, whereas cartilage- and bone-related proteins like aggrecan and chondroadherin appeared at day 60.
Real-time PCR revealed discordant regulation between messenger RNA and protein levels: gene expression was similar across border and injury zones, yet extracellular matrix proteins accumulated predominantly in the infarct area.

Structured PICO

P

Population

Porcine model of myocardial ischemia/reperfusion (2 hours of ischemia followed by 15 or 60 days of reperfusion) and validation in left ventricular tissue from patients with ischemic cardiomyopathy.

I

Intervention

Novel proteomic method to enrich for extracellular matrix (ECM) proteins (sequential extraction of soluble and insoluble fractions) analyzed by liquid chromatography tandem mass spectrometry (LC-MS) in infarcted and border zone regions of the left ventricle.

C

Comparator

Control animals without ischemia/reperfusion

O

Outcome

Identification and cataloging of cardiac extracellular matrix (ECM) proteins (the matridome) at 15 and 60 days post-ischemia/reperfusionsurrogate

Limitations

Prolonged 2-hour ischemia caused irreversible myocardial damage, examining infarcted rather than viable ischemic myocardium
Analysis was limited to 2 time points (15 and 60 days post-I/R) in a relatively small number of animals
ECM enrichment protocol does not likely solubilize the entire ECM, providing an incomplete representation
Non-infarcted remote region of hearts subjected to I/R was not analyzed
Animals did not receive standard post-MI medications (ACE inhibitors, beta-blockers, statins, antiplatelet agents, aldosterone inhibitors)
Prolonged (2 hour) episode of ischemia caused irreversible myocardial damage, examining infarcted rather than viable ischemic myocardium
ECM enrichment protocol does not likely solubilize the entire ECM, providing an incomplete representation of ECM composition
Cardiac tissue in the non-infarcted remote region of hearts subjected to I/R was not analyzed
Animals studied did not receive drugs routinely administered to patients post-MI (ACE inhibitors, beta-blockers, statins, antiplatelet agents, aldosterone inhibitors)

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Implication

Extracellular matrix proteomics of post-ischemia/reperfusion myocardium identifies 15 novel cardiac ECM proteins and provides candidate plasma biomarkers and therapeutic targets for post-MI cardiac remodeling.

Abstract

Prolonged myocardial ischemia leads to myocyte necrosis, which initiates a localized inflammatory response that catabolizes the cellular debris and initiates deposition of extracellular matrix (ECM) proteins.1 In addition to providing a vital structural framework for the three-dimensional organization of cells, the ECM determines the physical properties of biological tissues and acts as a dynamic microenvironment for cellular signaling. A number of cardiac diseases, including myocardial ischemia and reperfusion (I/R), are associated with qualitative and quantitative alterations in ECM proteins.2 Understanding ECM changes is important for identifying factors that tip the balance between favorable reparative remodeling following myonecrosis and adverse remodeling that leads to progressive ventricular dilatation and congestive heart failure. Article see p 789 ECM proteomics is the comprehensive description of the ECM expressed in a tissue at the time of evaluation. This approach generates a global, integrated view of extracellular processes and networks at the protein level. The goal of ECM proteomics is to reconcile gene activation to a particular extracellular phenotype. The ability to examine multiple proteins simultaneously is a substantial improvement over previous ECM studies that simply evaluated the total concentration of single proteins (ie, collagen) without consideration of type (eg, type I versus III versus IV) or quality (full-length versus partially degraded collagen). In this issue of Circulation , Barallobre-Barreiro and colleagues present an innovative extracellular matridomic approach for the analysis of ECM protein changes in a porcine I/R model.3 With the use of a novel proteomic method to enrich for ECM proteins, tissue from infarcted and border zone regions of the left ventricle (LV) were analyzed separately by liquid chromatography tandem mass spectrometry for peptide identification and compared with control animals without I/R. Using these techniques, they identified 139 ECM proteins in porcine hearts subjected to 2 hours of ischemia followed by …

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Cite This Study

DeLeon‐Pennell et al. (2012) conducted an editorial in Myocardial ischemia and reperfusion (I/R) / ischemic cardiomyopathy. Extracellular matrix (ECM) proteomic enrichment and liquid chromatography tandem mass spectrometry (LC-MS) analysis vs. Control animals without ischemia/reperfusion was evaluated on Identification of cardiac extracellular matrix (ECM) proteins post-ischemia/reperfusion. Extracellular matrix proteomics identified 139 ECM proteins, including 15 novel cardiac ECM proteins, in porcine hearts subjected to 2 hours of ischemia and 15 or 60 days of reperfusion.

synapsesocial.com/papers/6af4db05b2cba5828591f731 https://doi.org/10.1161/circulationaha.111.086835

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Extracellular Matrix Proteomics in Cardiac Ischemia/Reperfusion

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Extracellular Matrix Proteomics in Cardiac Ischemia/Reperfusion

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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