## 3 Cardiovascular Disease
### Myocardial Infarction
#### 3.3.2 Biology of Myocardial of Infarction  
Myocardial infarction involves a sudden and transient occlusion of the coronary arteries (either following acute atherosclerotic plaque rupture or a thrombo-embolic event), depriving the cardiomyocytes of vital nutrients and oxygen. The myocardial matrix network is primarily fibrillar collagen and is organised into three distinct interconnected structures: endomysium (surrounding cardiomyocytes), perimysium (surrounding major bundles) and the epimysium (encasing the whole cardiac muscle). Within these interconnected myocardial structures, there are different types of collagen, with the epimysium and perimysium containing approximately 85-90% type I and 6-11% type III collagen in the endomysium of the total collagen content [92]. The cardiac ECM has the structural role to preserve the shape of the ventricles, facilitate the translation of force and transduce signals [93]. Cardiomyocytes have no ability to regenerate and therefore, depending on the extent of  
Figure 14: Comparison of fluorescence signals from thrombi and the surrounding atherosclerotic plaque in the experimental group. HCD + MMP-ACPP **(a,b)** and HCD + Thrombin-ACPP(c). The images from left to right in **(a)** are: closed view fluorescence image, opened and zoomed-in fluorescence/reflected images with the thrombus (green arrows) attached at its original site, opened and zoomed-in fluorescence/reflected images with the thrombus removed. The dark signal of the aorta on the reflected image comes from clotted blood and relatively healthy vessel wall (without obvious fatty streaks). Plaques appeared as brighter (grey) signal. The bar graphs **(b,c)** give the statistical analysis of fluorescence signal for the underlying disrupted plaques (DP) and the overlaying thrombi (\(p<0.001\)). HCD—high cholesterol diet; ACPP—activatable cell penetrating Peptides. Reproduced with permission from [PERSON] et al., 2015 [84].  
the injury, the myocardial structural integrity can be severely disrupted with necrosed cardiomyocytesve replaced with fibrotic tissue leading to life-threatening arrhythmias and development of heart failure. After myocardial infarction (MI), MMPs are important in myocardial repair and scar formation, however if MMPs become excessively activated leading to an imbalance in MMP:TIMP ratio it can cause LV dysfunction and eventually lead to HF. The resulting insult subsequently triggers a cascade of molecular and cellular compensatory or damaging inflammatory, proliferative and maturation responses. The inflammatory phase is triggered by the death of cardiomyocyte cells that consequentially activates pro-inflammatory cytokines, enhancing the activity of MMPs promoting ECM degradation and also activates chemokines and other cell adhesion molecules. Neutrophils, leukocytes and macrophages are recruited into the infarcted area and as the debris is cleared from the area, the initial pro-inflammatory stimulus is suppressed by signals from mediators like interleukin-10 (IL-10) and transforming growth factor- \(\beta\) (TGF-\(\beta\)). These molecules, activate TIMPs that help preserve the ECM by inhibiting MMPs activity and initiate the proliferative phase [94]. During the proliferative phase, fibroblasts proliferate and transform/differentiate into myofibroblasts and secrete ECM proteins. The ECM subsequently undergoes extensive remodelling and cross-linking during the maturation phase leading to the formation of a fibrous scar. Fibroblasts are quiescent and along with endothelial cells they are also subjected to apoptosis at this stage [94]. Throughout the myocardial remodelling process, the ECM plays a crucial role and molecular imaging of specific ECM components could offer a wealth of diagnostic and therapeutic insights into heart failure post myocardial infarction that is an incredibly challenging clinical syndrome.