• adiponectin
• myocardial infarction
• extra-cellular matrix

ABSTRACT

Background. This study is a part of a wide project devoted to investigate the role of biochemical markers of cardiovascular disease, in order to better understand their molecular mechanisms. In this context, the knowledge of molecular response to cardiac injury constitutes an important tool for diagnosis and care of patients. Among molecular mechanisms underlying the response to cardiac injury, inflammation and extra-cellular matrix (ECM) remodeling represent essential processes during disease progression. Recently, a number of studies have suggested a relevant role of cardio-metabolic biomarkers, such as adipokines, in cardiovascular disease, specially as to their modification after cardiac injury.
Aim. The aim of this work was the evaluation of inflammatory and ECM remodeling processes in an experimental animal model of myocardial infarction (AMI). For this, inflammatory mediators, such as proinflammatory cytokines (IL-6, TNF-a), matrix metalloproteinases (MMP-2, -9), tissue inhibitors of matrix metalloproteinases (TIMP-1, -2) and collagen (COL3a) were evaluated at mRNA and protein level. In addition, adiponectin and its receptors, adipo-R1 and adipo-R2, were evaluated, owing the cardioprotective anti-inflammatory actions of adiponectin.
Methods. Left ventricular (LV) tissue was collected from male adult farm pigs with AMI (n=6), induced by permanent surgical ligation of the left anterior descending coronary artery. As control, 6 healthy adult farm pigs were also studied. Biomarker mRNA expression was determined by semi-quantitative RT-PCR in tissue samples collected from border (BZ) and remote zones (RZ) of infarcted area. Tissue concentrations were evaluated by Western Blotting analysis.
Results. After 1 week post-AMI, this surgical approach resulted in a permanent transmural infarction affecting 10-15% of the LV wall mass and, after 4 week, LVEF% was equal in infartcted animals as well as in control group (both > 50%). The mRNA expression of biomarkers, normalized on the respective GAPDH, was significantly higher in AMI than in controls, (MMP-9: 7.09±4.31; 1.18±0.28; 0.72± 0.11, respectively for BZ, RZ and controls, p <0.05 BZ vs. RZ and controls; TIMP-1: 2.41±1.20; 0.28±0.04; 0.33±0.05, p=0.01 BZ vs. RZ and controls; TIMP-2: 2.75±1.51; 0.53±0.04; 0.38±0.03, p<0.05 BZ vs. RZ and controls; COL3a: 4.28±1.11; 0.87±0.13; 0.61±0.18, p<0.001 BZ vs. RZ and controls). Inflammatory indices were both increased in animals with AMI without significant differences between BZ and RZ. The adiponectin is significantly increased compared with controls (2.95±1.69 vs. 0.52±0.12, p<0.05 BZ vs. controls) as well as the adipo-R1 (1.40±0.31 in the BZ vs. 1.26±0.20 in the RZ vs. 0.63±0.07 in controls, p<0.05 BZ e RZ vs. controls).
Conclusions. Our results show that the inflammatory and ECM remodelling processes are activated in this experimental model of AMI. Furthermore, the parallel activation of the system of adiponectin confirms the involvement of this adipokine in the process of cardiac remodelling/repair. The knowledge of the interaction between the various mediators of the complex response to cardiac damage could be an important target for the development and evaluation in animal models of new treatments of AMI which could be transferred to clinical practice.