Cardiac impairment Cardiomyocyte

Mice that lack caspase-1, -11, or -12 do not have a significant decrease in viability and have no overt consequence on their development [57-59,69,72]. In contrast, caspase-3 and/or -9 ablation results in retarded developmental apoptosis and has a tremendous impact on animals viability and phenotype [61, 67]. Similarly, caspase-8 knockout mice die in utero and are characterized by impaired formation of cardiac muscle and marked abdominal congestion with reduction of the number of hematopoietic precursors [65], The size of the heart was reported to be almost normal, but the developing ventricular musculature was thin and sometimes similar to early mesenchyme. The trabeculae were thin and disorganized. Cultured fibroblasts from caspase-8 mice were resistant to death receptor-mediated apoptosis. These findings indicate that caspase-8 plays an important role in death induction by several receptors of Fas/TNF/NGF family. Similarly, Sakamaki et al. [66] described that protease-deficient caspase-8 mutant mice died in utero due to heart rupture which they believe was due to cardiomyocyte apoptosis. 

Figure 15. Dose dependently c-GMP inhibits PDE or activates PKG, thereby mediating its effects on the vasculature, platelets and myocytes. The cardiac interstitial NO concentration during early ischemia and early reperfusion is increased. The increase in NO concentration is derived from activated NO synthase (NOS) isoforms (species specific) and from NOS independent pathways. Cardiac c-GMP concentration during ischemia is somewhat increased while upon reperfusion is decreased. NO seems to mediate protective as well as deleterious effects which are critically dependent on the specific experimental conditions. NO at lower concentrations preserves blood flow and attenuates platelet aggregation and neutrophil-endothelium interaction following ischemia and reperfusion. In small amounts might also be beneficial by nitration of the cardioprotective PKCe. Furthermore, NO increases cardiomyocyte function. Figure 16. At higher concentrations, NO depresses cardiomyocyte function, mediates inflammatory processes following ischemia and reperfusion, impairs mitochondrial respiration...

It should be noted that agonists of PLD simulate the effects of IP, whereas the inhibition of PLD blocks the beneficial effects of IP (Ozer et al., 2005 Hashizume et al., 1997). In summary, the two extremes of stress imposed on the heart under I-R change the redox potential of the cardiomyocyte and affect redox-sensitive molecules involved in phospholipid-mediated signal transduction mechanisms. The early activation of specific PLC and PLD isozymes may represent initiation of redox signaling and cell survival pathways, whereas inactivation of specific PLC and PLD isozymes may contribute to impaired cardiac contractile function (Fig. 11.6). 

In atherosclerosis, fatty material and cholesterol are deposited inside the lumen of medium- and large-sized blood vessels (arteries). Eventually, the plaque can rupture, triggering the formation of a blood clot. If the blood clot develops in the brain, it can cause a stroke if it develops in a coronary artery, it can cause a vessel occlusion and consequently a heart attack the supply of nutrients and oxygen to the heart muscle is reduced and the contractile muscle cells (cardiomyocytes) die within the blood-deprived myocardium. The tissue becomes necrotic and cardiac performances are impaired. 

---