Post Infarction Research Articles

A mitochondrial‐targeting peptide (Bendavia) decreases apoptosis and suppresses cardiac fibrosis in the noninfarcted border zone of infarcted hearts (1154.3)

Bendavia is a mitochondrial‐targeting peptide with cardioprotective properties. Apoptosis and cardiac fibrosis contribute to left ventricular remodeling in the post infarct state. We hypothesized that Bendavia decreases apoptosis and attenuates myocardial collagen deposition in the noninfarcted border zone (2 mm noninfarcted tissue on either side of scar). Starting 2 hours after left coronary artery ligation, rats were randomized to receive Bendavia (3 mg/kg/day), water or sham operation. At 6 weeks, TUNEL staining was performed to detect apoptosis. Picrosirius red staining and qRT‐PCR were used to analyze collagen deposition. TUNEL positive cells within the border zone were reduced by Bendavia (32 ± 3% of nuclei, n=12) vs the water group (41 ± 2%, n=12; p=0.029). Bendavia significantly suppressed collagen deposition, assessed by Picrosirius red staining, within the border zone (11 ± 1% of the area of border zone, n=28) vs water group (15 ± 1%, n=26; p=0.03). qRT‐PCR analysis showed that Col1a1, Col1a2 and Col3a1 gene expression were significantly increased by 4.76 fold, p=0.002, 2.85 fold, p=0.01 and 4.71 fold, p=0.019, respectively, in the water group vs sham. Importantly, Bendavia showed a trend of lowering these gene expression levels. We conclude that Bendavia decreases apoptosis and prevents cardiac fibrosis, which may have led to the preservation of cardiac function and structure.

Conditional Cardiac Overexpression of S100A6 Attenuates Myocyte Hypertrophy and Apoptosis Following Myocardial Infarction

S100A6, a 20 kDa, Ca2+ - binding dimer with low basal cardiac expression, is upregulated in the rat heart following infarction and forced expression of S100A6 in rat neonatal cardiac myocyte cultures, inhibited the induction of β myosin heavy chain (MHC), skeletal α actin (skACT) and myocyte apoptosis in response to diverse stimuli including tumor necrosis factor α. To define a role for S100A6 in vivo, we generated cardiac myocyte-specific transgenic mice by placing the human S100A6 cDNA downstream of a promoter responsive to a doxycycline (DOX)-regulated transcriptional activator (tTA) and breeding this line with one harboring cardiac myocyte-restricted (αMHC) expression of tTA (αMHC-tTA). We compared S100A6-αMHC-tTA mice 35 days post-myocardial infarction (MI) produced by coronary artery ligation with similar matched sham-operated controls on (S100A6 transgene overexpressed) or off (S100A6 transgene silenced) DOX. There were no differences between the sham groups on or off DOX. Thirty five days post-MI, myocardial S100A6 levels increased 12.5-fold in S100A6-α-MHC-tTA mice off DOX compared with S100A6-α-MHC-tTA mice on DOX. Hemodynamic studies, echocardiography and postmortem examination indicated that S100A6-αMHC-tTA mice on DOX 35 days post-MI mounted a hypertrophic response (20-22.5 % increase) accompanied by a program of fetal gene re-expression, fibrosis and myocardial apoptosis. Whereas the S100A6-α-MHC-tTA mice off DOX showed an attenuated myocyte hypertrophic response, less fibrosis and apoptosis which was beneficial to preservation of cardiac function. Therefore, S100A6 is a potential therapeutic target for modulation of adverse left ventricular remodeling in the early post infarct period.

DI-084 Acenocoumarol drug interactions in hospitalised patients

BackgroundAcenocoumarol interacts with widely-used drugs. In many cases, the result is an increase in the International Normalised Ratio (INR) which can have a significant clinical effect on patients.PurposeTo determine the...

Extracorporal membrane oxygenation: Perioperative support reduces the operative risk for post infarction ventricular septal defect

Introduction: Mechanical complications after acute myocardial infarction, such as ventricular defects (PI-VSD) are one of the most frequent causes of sudden cardiac death. This case report describes the perioperative management of a 55-year-old man with sub-acute PI-VSD.

Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction

Myocardial infarction (MI) provokes regional inflammation which facilitates the healing, whereas excessive inflammation leads to adverse cardiac remodelling. Our aim was to determine the role of macrophage migration inhibitory factor (MIF) in inflammation and cardiac remodelling following MI. Wild type (WT) or global MIF deficient (MIFKO) mice were subjected to coronary artery occlusion. Compared to WT mice, MIFKO mice had a significantly lower incidence of post-MI cardiac rupture (27% vs. 53%) and amelioration of cardiac remodelling. These were associated with suppressed myocardial leukocyte infiltration, inflammatory mediators' expression, and reduced activity of MMP-2, MMP-9, p38 and JNK MAPK. Infarct myocardium-derived or exogenous MIF mediated macrophage chemotaxis in vitro that was suppressed by inhibition of p38 MAPK or NF-κB. To further dissect the role of MIF derived from different cellular sources in post-MI cardiac remodelling, we generated chimeric mice with MIF deficiency either in bone marrow derived-cells (WTKO) or in somatic-cells (KOWT). Compared to WT and KOWT mice, WTKO mice had reduced rupture risk and ameliorated cardiac remodelling, associated with attenuated regional leukocyte infiltration and expression of inflammatory mediators. In contrast, KOWT mice had delayed healing and enhanced expression of M1 macrophage markers, but diminished expression of M2 markers during the early healing phase. In conclusion, global MIF deletion protects the heart from post-infarct cardiac rupture and remodelling through suppression of leukocyte infiltration and inflammation. Leukocyte-derived MIF promotes inflammatory responses after MI, whereas cardiac-derived MIF affects early but not ultimate healing process.

Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats

Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12U/d for 7 days) 24h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction.

Abstract 9912: Global Intracoronary Infusion of Allogeneic Atrial Cardiosphere-Derived Cells (CDCs) Stimulates Myocyte Regeneration and Reverses LV Remodeling in Miniature Swine With Chronic Myocardial Infarction

Background: Intracoronary infusion of autologous CDCs (icCDCs) into the infarct-related artery using the “stop flow” technique improves regional function in patients but global function remains unchanged. We tested the hypothesis that this reflects the inability to regress cellular hypertrophy and replace myocytes lost in remote remodeled regions that can be overcome by global intracoronary infusion of CDCs. Methods: Miniswine (n=10) were studied 8 weeks after chronic infarction was produced by LAD microembolization (1x10 6 microspheres, 45μm diameter). Ejection fraction decreased from 63 ± 2% at baseline to 31 ± 2% four weeks after infarction (p<0.05 vs. baseline) and remained unchanged at 8 weeks (32 ± 2%, p-ns vs. 4 weeks). Allogeneic CDCs (20 x 10 6 CDCs, cyclosporine 100 mg/day) isolated from donor atrial biopsies were infused into the 3 major coronary distributions without interrupting flow. We assessed myocardial function (echo), myocyte proliferation (Ki67) and infarct size (TTC) in comparison to untreated controls. Regional myocyte regeneration was quantified by assessing myocyte nuclear density and size. Results: Infusing icCDCs into infarcted and remodeled remote myocardium increased regional function and ejection fraction (Table). icCDCs stimulated myocyte proliferation (Ki67) in LAD and remote regions by three-fold. As a result, myocyte number (nuclear density) increased by 35% and myocyte cell diameter decreased by 33% in both LAD and remote myocardium. The reduction in infarct volume after icCDCs was not significant. Conclusion: We conclude that global infusion of allogeneic icCDCs without “stop flow” 1.) stimulates myocyte proliferation throughout the LV and 2.) in a model of infarction, improves regional function with a substantial increase in left ventricular ejection fraction. Thus, allogeneic icCDCs may afford a widely available platform to reverse LV dysfunction in patients with chronic post infarction LV remodeling.

Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after acute cerebral infarction.

Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we induced a photochemical model of cerebral infarction in an inbred line of mice (BALB/c). Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hy-Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.

Genetically modified human myoblasts with eNOS may improve regenerative ability of myogenic stem cells to infarcted heart

Modern therapies of post infarcted heart failure are focused on perfusion improvement of the injured myocardium. This effect can be achieved by, among other means, implanting stem cells which could be genetically modified with factors inducing the formation of new blood vessels in the post infarction scar area. Combined stem cell and gene therapy seems to be a promising strategy to heal an impaired myocardium. The creation of new blood vessels can be indirectly stimulated via factors inducing vascular endothelial growth factor synthesis, for example endothelial nitric oxide synthase (eNOS). The product of this enzyme, nitric oxide, is a molecule that can influence numerous physiological activities; it can contribute to vasodilation, stimulation of endothelial cell growth, prevention of platelet aggregation and leukocyte adhesion to the endothelium. To verify the pro-angiogenic and regenerative potential of human primary myoblasts and murine myoblast cell line C2C12 transiently transfected with eNOS gene. Stem cells (either human or murine) were maintained in standard in vitro conditions. Next, both types of myoblasts were modified using electroporation and lipofection (human and murine cells), respectively. The efficacy of the transfection method was evaluated using flow cytometry. The concentration of eNOS protein was measured by ELISA immunoassay. The biological properties of modified cells were assessed using an MTT proliferation test and DAPI cell cycle analysis. To verify the influence of oxidative stress on myoblasts, cytometric tests using Annexin V and propidium iodide were applied. To check possible alterations in myogenic gene expression of stem cells transduced by genetic modification, the myogenic regulatory factors were evaluated by real-time PCR. The function of genetic modification was confirmed by a HUVEC capillary sprouting test using myoblasts supernatants. Electroporation turned out to be an efficient transfection method. High amounts of secreted protein were obtained (in the range 2,000 pg/mL) in both cell types studied. Moreover, the functionality of gene overexpression product was confirmed in capillary development assay. Human myoblasts did not exhibit any changes in cell cycle; however, eNOS transfected murine myoblasts revealed a statistically significant reduction in cell cycle ratio compared to controls (p < 0.001). In the case of myogenic gene expression, a decrease in Myogenin level was only detected in the human transfected myoblast population (p < 0.05). The results of our study may suggest that transplantation of myoblasts overexpressing eNOS could be promising for cell therapy in regenerating the post infarction heart.

Ankyrin-G Participates in INa Remodeling in Myocytes from the Border Zones of Infarcted Canine Heart

Cardiac Na channel remodeling provides a critical substrate for generation of reentrant arrhythmias in border zones of the infarcted canine heart. Recent studies show that Nav1.5 assembly and function are linked to ankyrin-G, gap, and mechanical junction proteins. In this study our objective is to expound the status of the cardiac Na channel, its interacting protein ankyrinG and the mechanical and gap junction proteins at two different times post infarction when arrhythmias are known to occur; that is, 48 hr and 5 day post coronary occlusion. Previous studies have shown the origins of arrhythmic events come from the subendocardial Purkinje and epicardial border zone. Our Purkinje cell (Pcell) voltage clamp study shows that INa and its kinetic parameters do not differ between Pcells from the subendocardium of the 48hr infarcted heart (IZPCs) and control non-infarcted Pcells (NZPCs). Immunostaining studies revealed that disturbances of Nav1.5 protein location with ankyrin-G are modest in 48 hr IZPCs. Therefore, Na current remodeling does not contribute to the abnormal conduction in the subendocardial border zone 48 hr post myocardial infarction as previously defined. In addition, immunohistochemical data show that Cx40/Cx43 co-localize at the intercalated disc (IDs) of control NZPCs but separate in IZPCs. At the same time, Purkinje cell desmoplakin and desmoglein2 immunostaining become diffuse while plakophilin2 and plakoglobin increase in abundance at IDs. In the epicardial border zone 5 days post myocardial infarction, immunoblot and immunocytochemical analyses showed that ankyrin-G protein expression is increased and re-localized to submembrane cell regions at a time when Nav1.5 function is decreased. Thus, Nav1.5 and ankyrin-G remodeling occur later after myocardial infarction compared to that of gap and mechanical junctional proteins. Gap and mechanical junctional proteins remodel in IZPCs early, perhaps to help maintain Nav1.5 subcellular location position and preserve its function soon after myocardial infarction.

Acute afterload increase causes mechanical dispersion — potential mechanism for pressure induced arrhythmias?

Cardiologia CROATICA Objectives: We have recently shown that an acute afterload increase of the left ventricle induces premature ventricular beats (PVB). We explored mechanical dispersion, which has recently been linked to a greater incidence of arrhythmias in post infarction ICD patients, as a potential underlying mechanism. Methods: 7 closed chest, closed pericardium pigs were instrumented with an aortic balloon in the mid-thoracic descending aorta. Parasternal long-axis B-mode images were acquired before and during the balloon inflation (N=22), causing a 30% increase in systolic blood pressure and an acute LV dilatation over 5-10 beats. Before and during inflation, segmental septal deformation was analyzed using speckle tracking and timing and the amount of peak strain were measured. Mechanical dispersion was calculated as the standard deviation (SD) of the time to peak strain in the three segments. 12 lead ECG was acquired in all animals. Results: PVBs occurred in 33% of the pressure challenges. The afterload increase caused a visible dispersion in the timing of the strain curves of the three segments (Figure 1a). Despite no change in QT interval, mean time of peak strain increased from 291±81 ms, in preinflation to 352±56 ms during inflation in the three segments, resulting in postsystolic shortening. The SD increased significantly from preinflation to inflation (p=0.02) (Figure 1b). While strain at aortic valve closure clearly went down with afterload (-14.74±6 to -11.04±4.02, p=0.0001), peak shortening remained similar (-15.79±6.09 to -15.12±4.56, p=0.479). Conclusion: Acute afterload increase of the LV significantly increased the difference in time to peak strain between the three septal segments, resulting in increased mechanical dispersion, which may play a role in pressure-induced arrhythmias.

The prevalence of heart problems and risk factors in patient with ischemic stroke and their relationship with severity of stroke

The prevalence of heart problems and risk factors in patient with ischemic stroke and their relationship with severity of stroke

Utilisation of sphericity indices in the assessment of left ventricular shape and function after surgical ventricular restoration in patients recovered from anterior myocardial infarction

Background Surgical ventricular restoration (SVR) after anterior myocardial infarction with post infarction aneurysm, significantly improves left ventricular (LV) performance. To describe mid-term postoperative changes of shape and performance of the newly created LV and mitral valve function through the classical (SI) and apical (ASI) left ventricular sphericity index, and determinants of mitral regurgitation.

The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction

Regeneration of the damaged myocardium is one of the most challenging fronts in the field of tissue engineering due to the limited capacity of adult heart tissue to heal and to the mechanical and structural constraints of the cardiac tissue. In this study we demonstrate that an engineered acellular scaffold comprising type I collagen, endowed with specific physiomechanical properties, improves cardiac function when used as a cardiac patch following myocardial infarction. Patches were grafted onto the infarcted myocardium in adult murine hearts immediately after ligation of left anterior descending artery and the physiological outcomes were monitored by echocardiography, and by hemodynamic and histological analyses four weeks post infarction. In comparison to infarcted hearts with no treatment, hearts bearing patches preserved contractility and significantly protected the cardiac tissue from injury at the anatomical and functional levels. This improvement was accompanied by attenuated left ventricular remodeling, diminished fibrosis, and formation of a network of interconnected blood vessels within the infarct. Histological and immunostaining confirmed integration of the patch with native cardiac cells including fibroblasts, smooth muscle cells, epicardial cells, and immature cardiomyocytes. In summary, an acellular biomaterial with specific biomechanical properties promotes the endogenous capacity of the infarcted myocardium to attenuate remodeling and improve heart function following myocardial infarction.

Motivational interviewing as educational program in improving cardiac risk factors control in patients post myocardial infarction

Introduction: Motivational interviewing (MI) is a counseling style that was developed as an alternative to more traditional counseling using direct persuasion. It uses the patient's responses to reinforce talk directed toward change. The study examines MI as a tool for promoting lifestyle change in patients post infarction particularly smoking cessation, decrease saturated fat intake and increase physical activity. Methods: 1850 post myocardial infarction patients were recruited over 2 years period and were randomly assigned to either usual follow up or MI educational program. Patients participated in a 30 min weekly education session for eight weeks. Follow up telephone calls after another 4 weeks. Results: After MI, 95% of patients reported self cessation of smoking versus 75% in usual care patients (p<0.05). Awareness as regards overweight was increased, and 45% took active steps to reduce their weight versus 12% in usual care (p<0.05). Awareness to diet modifications has improved and 88% took active steps to reduce saturated fat versus 43% in usual care (p<0.05). After MI, 56% took active steps to increase their physical activity versus 32% in usual care (p<0.05). Conclusion: MI can promote behavior change in patients post infarction and is advisable to integrate in rehabilitation program.

Transcatheter closure of an inferior post infarction ventricular septal defect using a customised device

Transcatheter closure of an inferior post infarction ventricular septal defect using a customised device

GW24-e1356 The histocompatibility of angiotensin converting enzyme does not promote its function on inhibitory to negative ventricular remodelling

ObjectivesRenin-angiontensin-aldosterone system (RAAS) is widely evidenced its point on inhibiting ventricular remodelling post myocardial infarction. The increasing expression of angiotensin and angiotensin-converting enzyme (ACE) post infarction and the effectiveness of...

043 MONOCYTE SUBPOPULATION COUNTS AND ASSOCIATIONS WITH LEFT VENTRICULAR EJECTION FRACTION POST ST ELEVATION MYOCARDIAL INFARCTION: Table 1

<h3>Background</h3> Monocytes are implicated in the initiation and progression of the atherosclerotic plaque contributing to plaque instability and rupture. Little is known about the role of the three phenotypically and functionally different monocyte subpopulations in determining ventricular remodelling following ST elevation myocardial infarction (STEMI). Mon1 are the ‘classical’ monocytes with inflammatory action, whilst Mon3 are considered reparative with fibroblast deposition ability. The function of the newly described Mon2 subset is yet to be fully described. <h3>Method</h3> STEMI patients (n=196, mean age 62±13 years; 72% male) treated with percutaneous revascularization were recruited within the first 24 h post-infarction. Peripheral blood monocyte subpopulations were enumerated and characterised using flow cytometry after staining for CD14, CD16 and CCR2. Phenotypically, monocyte subpopulations are defined as: CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3) cells. Transthoracic 2D echocardiography was performed within 7 days and at 6 months post infarct to assess ventricular volumes, mass, systolic, and diastolic functions as well as strain and strain rate. <h3>Results</h3> Using linear regression analysis higher counts for Mon1, and lower counts for Mon2 and Mon3 were significantly associated with the baseline left ventricular ejection fraction (LVEF) within 7 days post infarct (table&nbsp;1). At 6 months post STEMI lower counts of Mon2 remained positively associated with a decrease in LVEF at completion of remodelling (p=0.002). <h3>Conclusion</h3> Peripheral monocytes of all three subsets correlate with LVEF after a myocardial infarction. High counts of the inflammatory Mon1 are associated with the reduced baseline ejection fraction post infarction. After remodelling, the convalescent ejection fraction was independently predicted by monocyte subpopulation 2. As lower counts depicted negative ventricular remodelling, this suggests a possible myofibroblast deposition and angiogenesis role for the newly described intermediate monocyte subpopulation Mon2 as opposed to the previously anticipated inflammatory role.

Finite element analysis regarding patch size, stiffness, and contact condition to the endocardium in surgery for post infarction ventricular septal rupture

The purpose of this study is to establish a rational surgical design to minimize suture line stress of the patch and thus prevent residual leakage in surgery for post infarction ventricular septal rupture (VSR). A computer model that simulates surgery for VSR was developed. Stress force on the suture line of the patch was calculated at varying size, stiffness, and contact condition of the endocardial patch to the inner surface of the heart using a finite element analysis. Clinical results and echo findings of 34 consecutive patients with a mean age of 72.6±9.5 (range 55-89) who underwent emergency surgery for VSR from 1995 to 2012 were reviewed. Suture line stress decreased by two-thirds as the size or stiffness of the patch increased in comparison with the basic conditions that mimic a pericardial patch fitted to the septal plane. On the other hand, suture line stress increased sixfold when there was a dead space beneath the patch. 30-day mortality was 12%, and in-hospital mortality 18%. On echocardiography, all three patients who had dead space beneath the patch had residual leak. Another patient who had huge posterior defect also showed residual leak. Clinical results were well matched to model results. 5-year survival rate of all patients who received operation was 68.7±9.3%. In endocardial patch type surgery for VSR, proper sizing of the patch to sufficiently fit to endocardial surface in a tension-free condition is the most important to avoid residual leak.

ASSA13-03-45 Effects from Age to Wnt and NF-kB Signal Pathway in Heart of Mice

<h3>Background</h3> Wnt and NF-κB signal pathway are all related to cardiac remodelling post-infarction and there were age-related differences of outcome post infarction. We study changes of these two signal pathways in heart in old mice to prepare some materials for advanced study. <h3>Methods</h3> We used 20 mice to study changes of these two signal pathways: 10 in young (3-mo) and old group (18-mo) respectively. They were detected expression of dvl-1, β-catenin, p/t GSK-3β and connexin 43 in the left ventricle (LV) by western-blot. And they were detected expression of p65 and p50 by immunohistochemistry and western-blot. At the same time they were detected expression of ICAM-1 and VCAM-1. <h3>Results</h3> (1) Expression of dvl-1 increased by 2.41 fold in old group compared with young mice in the LV (<i>P</i> = 0.000). There were no statistically differences of expression of β-catenin between the old and young group (<i>P</i> = 0.647) in LV. Ratio of p/t GSK-3β is much lower in old compared with young (<i>P</i> = 0.000). When talking about connexin 43, there were statistically significant differences in old group compared with young (<i>P</i> = 0.001) in the LV. (2) There was no difference of numbers of p65 and p50 positive cells between old and young group by immunohistochemistry (<i>P &lt;</i> 0.05). But expression of p65 and p50 in nuclear protein in old group is higher than it in young group (<i>P</i> = 0.000). There was no difference of ICAM-1 between old and young group (<i>P</i> = 0.401). Expression of VCAM-1 in old group was higher than it in young group (<i>P</i> = 0.000). <h3>Conclusions</h3> There were age-related differences of protein associated with Wnt and NF-κB signal pathway in heart. Progressing study about changes in these two signal pathway post myocardial-infarction might find new mechanisms about age-related differences of cardiac remodelling.