Analysis of the Plasma Proteome Associated with Acute Coronary Syndrome: Does a Permanent Protein Signature Exist in the Plasma of ACS Patients?

Abstract

Acute coronary syndrome (ACS) is triggered by the occlusion of a coronary artery usually due to the thrombosis caused by an atherosclerotic plaque. The identification of proteins directly involved in the pathophysiological events underlying ACS will enable more precise diagnoses and a more accurate prognosis to be determined. Accordingly, we have performed a longitudinal study of the plasma proteome in ACS patients by 2-DE and DIGE. Plasma samples from patients, healthy controls, and stable coronary artery disease (CAD) patients were immunodepleted of the six most abundant proteins, and they were analyzed in parallel at four different times: 0 (on admission) and after 4, 60, and 180 days. From a total of 1400 spot proteins analyzed, 33 proteins were differentially expressed in ACS patients when compared with control subjects/stable patients. A small group of seven proteins that appear to be altered at admission remain affected for 6 months and also in the stable CAD patients. Interestingly, the maximum number of altered proteins was observed in the stable CAD patients. Some of the proteins identified had been previously associated with ACS whereas others (such as Alpha-1-B-glycoprotein, Hakata antigen, Tetranectin, Tropomyosin 4) constitute novel proteins that are altered in this pathology.

Modification of the Secretion Pattern of Proteases, Inflammatory Mediators, and Extracellular Matrix Proteins by Human Aortic Valve is Key in Severe Aortic Stenosis

“…Given that PTX3 is predominantly released by inflamed tissue in response to proinflammatory cytokines (TNF-␣ and IL-1␤) (47) and, considering the recent proposal that AS may be an inflammatory disease, our findings would be consistent with this hypothesis, because PTX3 secretion was increased in AS valves. Secretion of clusterin protein was much lower in AS valves, in agreement with previous findings in ACS plasma (48), which highlights the occurrence of numerous alterations in protein expression common to both atherosclerosis and AS. Clusterin is a glycoprotein whose function remains unclear, although it has been implicated in complement regulation (49), acute phase response (50), lipid transport (51), apoptosis (52), and membrane protection at the tissue-fluid interface where it is expressed.…”

Implementation strategies of Systems Medicine in clinical research and home care for cardiovascular disease patients

“…More recently, the development of clinically-applied mass spectrometry techniques [34] has further broadened the systems approach to CVD. By screening a large amount of different potential biomarkers, both proteomics (Table 2) [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] and metabolomics (Table 3) [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] studies aimed at improving knowledge of CVD pathways. However, many factors precluded meaningful biological insights or practical prediction so that the value of these recent discoveries was currently viewed with skepticism [69].…”

“…Dardé et al [41] 2010 Case-control (40 AMI, 10 CAD and 10 healthy controls) 1400 protein analyzed by 2-DE and 2DIGE at different time points…”

The Path to Personalized Cardiovascular Medicine

“…258,[281][282][283] Plasma proteomics using various MS-based technologies has recently been applied to identify protein biomarkers associated with CAD, peripheral artery disease (PAD) and acute coronary syndrome (ACS). [284][285][286][287] Urine MS proteomic analysis has revealed protein signatures specific for CAD. 288,289 This approach allows detecting CAD patients with high confidence and monitoring outcomes of therapeutic treatment.…”