Relationship between the oxidative stress biomarkers and coronary heart disease: Pathogenesis to therapeutic aspects

Table 1 The circulating levels of oxidative stress biomarkers in the pathogenesis of coronary heart disease

Oxidative stress biomarkers	Pathogenesis in CHD
Paraoxonase	↓
Nitrotyrosine	↑
Glutathione peroxidase	↨
Advanced glycation end products	↑
8-hydroxydeoxyguanosine	↑
Myeloperoxidase	↑
Extracellular superoxide dismutase	↓
SOD1, SOD2	↑
Malondialdehyde	↑
F2-isoprostanes	?
Catalase activity	?
Derivatives of reactive oxidative metabolites	↑

CHD: Coronary heart disease; SOD: Superoxide dismutase; ↑: Increased levels; ↓: Decreased levels; ?: Not reported yet; ↨: Not sure increased or decreased levels.

Table 2 Oxidative stress biomarkers cause pathogenesis in coronary heart disease

Oxidative stress biomarkers	Pathogenesis in CHD	Ref.
PON1	Low PON activity reduces the ability of HDL to prevent LDL oxidation, enhancing foam cell formation and atherogenesis. A key player in the oxidation of LDL and the inhibition of coronary atherogenesis is PON1. There is a direct correlation between low serum PON1 activity and CHD	[23,26]
Nitrotyrosine	Elevated levels indicate endothelial dysfunction and vascular inflammation, contributing to plaque instability. Oxidant production and immune system activation in CAD are related because posttranslational modification of proteins through nitration acts as a neo-epitope for the elaboration of immunoglobulins in atherosclerotic plaque-filled arteries and in circulation	[30,33]
Advanced glycation end products	Explained in Figure 1
GPx	Reduced GPx activity weakens antioxidant defense, allowing oxidative damage to endothelial cells and vascular tissues	[35-37]
8-OHdG	Elevated 8-OHdG reflects oxidative DNA injury in vascular cells, which might lead to apoptosis, impaired repair, and vascular remodeling	[45]
MPO	MPO promotes LDL oxidation, endothelial dysfunction, and plaque vulnerability. MPO and MPO-derived oxidants have a role in the production of foam cells, endothelial dysfunction and death, latent matrix metalloproteinases activation, and tissue factor expression, all of which might encourage the creation of susceptible plaque	[12]
SOD	Reduced SOD activity increases superoxide accumulation, impairing nitric oxide bioavailability, causing endothelial dysfunction. Endothelial dysfunction in CAD patients is exacerbated by decreased EC-SOD activity	[63]
MDA	Elevated MDA levels reflect oxidative damage to lipids, promoting LDL modification and atherosclerosis. High blood levels of malondialdehyde show that oxygen-free radicals are being produced at a higher rate, which may contribute to atherogenesis and coronary heart disease	[69]
F2-isoprostanes	Not determined
Catalase activity	Not determined
Derivatives of reactive oxidative metabolites	The development of CAD is linked to the generation of DROM in the coronary circulation. Patients with CAD had higher DROM, which is linked to subsequent cardiovascular events	[80]

CHD: Coronary heart disease; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; CAD: Coronary artery disease; DROM: Derivatives of reactive oxidative metabolites; EC-SOD: Extracellular superoxide dismutase; MDA: Malondialdehyde; GPx: Glutathione peroxidase; 8-OHdG: 8-hydroxydeoxyguanosine.

Table 3 Overview of therapeutic approaches in coronary heart disease

Biomarkers	Therapeutic aspects in CHD	Ref.
PON1	A lot of research is being done on PON1, and it is hoped that new treatment strategies will be developed to boost its activity. If successful, clinical studies of these will not only offer a new way to prevent atherosclerosis but also a more satisfactory way to test the oxidant theory of atherosclerosis than antioxidant vitamin supplementation has. PON-1 activity highlights the pathway's importance in vascular illness and supports its suggested function as a target to alter and assess cardiovascular risk. HDL-targeted therapies may improve PON activity	[23,25]
Nitrotyrosine	Nitrotyrosine levels are linked to CAD and seem to be influenced by statin medication. Atherosclerosis risk assessment and the monitoring of statins' anti-inflammatory effects may be affected by these findings, which point to a possible role for nitric oxide-derived oxidants as inflammatory mediators in CAD. Lowering nitrosative stress by antioxidants may reduce nitrotyrosine formation	[31]
AGE	The AGE-RAGE axis may be successfully disrupted by preventing AGE synthesis, preventing RAGE from attaching to its ligands, or suppressing RAGE expression, which would postpone or improve the aforementioned disorders. Both AGE and sRAGE, the soluble receptor for advanced glycation end products, may be new indicators of heart disease	[42]
MPO	Chaikijurajai and Tang[87] look at the pathophysiology of atherosclerotic CAD and the mechanistic information from a number of important therapeutic medication targets. The enzymatic activities of MPO are either directly or indirectly attenuated by prototype compounds, such as aminobenzoic acid hydrazide, ferulic acid derivative (INV-315), thiouracil derivatives (PF-1355 and PF-0628999), 2-thioxanthine derivative (AZM198), triazolopyrimidines, acetaminophen, N-acetyl lysyltyrosylcysteine (KYC), flavonoids, triazolopyrimidines, and alternative substrates like thiocyanate and nitroxide radicals. The cardiovascular advantages of direct systemic inhibition of MPO must be evaluated in future research to see if they exceed the danger of immunological dysfunction, which may be lower with other substrates or MPO inhibitors that specifically reduce MPO's atherogenic effects	[87]
SOD	Exercise, a diet rich in antioxidants, and statins can improve SOD activity. SOD modulation may prevent endothelial dysfunction and delay atherosclerosis progression	[62]
MDA	A dependable, non-invasive biomarker for CAD severity prediction, elevated serum MDA may find use in clinical risk assessment and therapy plans. Early detection of individuals with high oxidative stress allows doctors to intervene promptly, which may delay the course of the disease and improve prognosis. Elevated serum level MDA is a trustworthy, non-invasive biomarker for CAD severity prediction, and it may find use in clinical risk assessment and management plans. Clinicians may be able to decrease the course of the disease and improve outcomes by promptly implementing therapies for individuals with high oxidative stress	[66,68]
F2-isoprostanes	F2-isoprostanes are helpful biomarkers that may be used as CHD indicators	[74]
Catalase	Innovations in gene therapy, protein engineering, and nanotechnology are expected to propel major breakthroughs in the catalase enzyme's future. Through the use of gene-editing tools, protein engineering methods, and nanoparticle-based delivery systems, catalase's stability, bioavailability, and targeted administration for therapeutic reasons may all be significantly increased. Using computational models for predictive enzyme design, exploring possible synergy with other antioxidants, and tailoring catalase variations to meet particular therapeutic needs are all intriguing approaches to maximizing the therapeutic efficacy of catalase. A new area of study is examining the possible use of catalase as a prognostic or diagnostic biomarker in oxidative stress-related disorders. The complex and ever-changing future prospects of catalase highlight its vital role in advancing disease preventive techniques, advancing customized treatment initiatives, and eventually improving healthcare outcomes. In order to transform treatment interventions and provide comprehensive healthcare solutions for a range of patient groups, catalase is at the forefront of creative techniques by integrating cutting-edge technology and investigating novel applications	[85,86]
DROMs'	Furthermore, d-ROMs' clinical importance will be better understood by cross-comparison with other oxidative-stress biomarkers and their inclusion in sizable panels of biomarkers linked to CVD. Finally, to comprehend the potential use of d-ROMs in promoting more individualized therapeutic methods, additional research should be done on the effects of hereditary variables and pharmaceutical therapies on d-ROM levels. DROM may offer therapeutic advantages for CAD risk assessment	[79,80]

CHD: Coronary heart disease; HDL: High-density lipoprotein; CAD: Coronary artery disease; DROM: Derivatives of reactive oxidative metabolites; SOD: Superoxide dismutase; MDA: Malondialdehyde; AGE: Advanced glycation end-products; RAGE: Advanced glycation end-products with their receptor.