Oxidative Stress in Ischemic Heart Disease

Table 1

Discussed pharmacological therapeutic possibilities in ischemic heart disease.

Reference	Study characteristic	Therapeutic options	Primary endpoint
Zhang X et al. [242]	Experimental study on animal models such as rat	Aspirin (platelet inhibitors)	Enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways
Rodius et al. [263]	In vitro studies of mammalian cardiac cell models	Fisetin (plant polyphenol from the flavonoid group)	Reduction of ROS production, protects from DNA damage
Verma et al. [265]	Experimental study on male albino Wistar rats	Morin (bioflavonoid)	Regulation of RISK/SAPK pathways
Syeda et al. [266]	Experimental study on mice	Anthocyanidins (plant pigments)	Inhibition of ROS/p-JNK/Bcl-2 pathway
Flather et al.; Ambrosio et al. [223, 224]	Randomized trial in elderly patients with heart failure	Nebivolol (beta-1-selective blocker), beta(3)-adrenoreceptor agonistic effect	Stimulates eNOS, NO release, vasodilatation
Mihai et al. [222]	Randomized trial in patients with heart failure and reduced ejection fraction	Vericiguat (a soluble guanylate cyclase stimulator)	Changes in the NT-proBNP level have not been achieved, but the phase III trial is ongoing
McMurray et al. [226]	Randomized, double-blind trial in patients with heart failure and reduced ejection fraction	Sacubitril/valsartan (NP degradation inhibitor/angiotensin II receptor inhibitor) vs. enalapril	Increase cGMP, vasodilatation
Solomon et al. [227]	Randomized, double-blind study in a phase II trials, in patients with heart failure and reduced ejection fraction	Sacubitril/valsartan (NP degradation inhibitor/angiotensin II receptor inhibitor) vs. valsartan	Changes in NT-proBNP
Carmine et al. [228]	Randomized, prospective, single-blind, placebo-controlled fashion in patients who have chest pain and angiographically normal epicardial vessels	Ramipril (ACE inhibitor) and atorvastatin (statins)	Reduced SOD activity, low superoxide anion level
Amir et al. [245]	Randomized study, double- blind in patients with patients without significant CAD on coronary angiography	L-arginine (substrate for NO synthase)	Improve endothelial function, increase NO and NO inhibits the production of endothelin via cGMP pathway
Martin et al. [247]	Single-center, double-blind, randomized controlled trial in patients with CMD	Atrasentan (ETA receptor antagonist)	Supports the role of the endogenous endothelin system

eNOS: endothelial nitric oxide synthase; NO: nitric oxide; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; cGMP: cyclic guanosine monophosphate; ACE inhibitor: angiotensin converting enzyme inhibitors; SOD: superoxide dismutase; Hsp90: heat shock proteins 90; PI3K/Akt: phosphoinositide-3-kinase–protein kinase; PKM2: M2 isoform of pyruvate kinase; ETA receptor: endothelin-A receptor; CMD: coronary microvascular dysfunction; ROS: reactive oxygen species; RISK/SAPK pathway: extracellular regulated kinase (ERK), protein kinase A (Akt) and eNOS/p38 proteins, and c-Jun N-terminal kinase (JNK); ROS/p-JNK/Bcl-2 pathway: reactive oxygen species/stress-activated c-Jun N-terminal kinase/B-cell lymphoma.