Biomarkers of Oxidative Stress in Heart Disease

February is marked as “Heart Month” drawing attention to heart disease and its prevention. Cardiovascular diseases (CVD) are the leading cause of death globally with an estimated toll of 17.9 million people per year (1).

Unhealthy diet, physical inactivity, tobacco use are only some of the  behavioral risk factors associated with heart disease. Health conditions that increase the risk include obesity, elevated blood sugar levels, high blood pressure, high low-density lipoprotein (LDL) cholesterol, and oxidative stress.

Biomarkers of Oxidative Stress in Heart Disease

What is oxidative stress?

 

Oxidative stress is caused by an imbalance between the production of free radicals (reactive oxygen species- ROS) and antioxidant defenses (endogenous antioxidant capacity). ROSs are generated as metabolic by-products in cells that can be stimulated by a variety of agents including pollutants, heavy metals, tobacco, drugs and many other. It has been postulated that oxidative stress can be responsible in the onset and progression of several diseases (e.g. cancer, diabetes, metabolic disorders, atherosclerosis, and cardiovascular diseases) (2).

Oxidized LDL (oxLDL) and Anti-oxidized LDL Autoantibodies

Accumulation of oxidized-low density lipoproteins (oxLDL) in the blood vessels triggers the onset of atherosclerosis which is a key element of the development of cardiovascular disease (CVD). The term atherosclerosis is of Greek origin, meaning thickening of the intimal layer of arteries and accumulation of fat (3). The process of atherosclerosis is initiated by LDL particles that lie in the sub-endothelial space of arteries (4). Thus, atherosclerosis is a disease of the vascular intima as a result of lipid oxidation. In the later stages of disease progression, plaques build up that rupture resulting in thrombosis (blockage of blood flow). oxLDL induces inflammatory responses in macrophages and dendritic cells (5).

Autoantibodies against oxidatively modified LDL (anti-oxLDL Ab)  have been detected in patients with atherosclerosis as well as in healthy individuals (6). It has been suggested that they mirror the occurrence of oxidation processes taking place in vivo. Anti-oxLDL Ab can be measured in human blood samples with a conventional ELISA assay (6-8). Numerous studies have implied that autoantibodies to oxLDL may allow improved CV risk stratification (6).

How can oxidative status / oxidative stress be measured?

 

Oxidative stress can be measured indirectly by different techniques. 

Example of a BIOMEDICA ELISA kit

 

1.MEASUREMENT OF ANTI-OXIDIZED LDL AUTOANTIBODIES 

ELISA for the detection of Anti-oxidized LDL Autoantibodies (oLAB ) | BI-20032

• Sample type: serum
• Sample volume 50µl/well
• Incubation time: 1.5 h / 30 min / 15 min
• Detection range: 0 – 1200 mU / ml
• Sensitivity: 48 mU / ml
• Precision: In-between-run (n=5): ≤ 8 % CV, Within-run (n=8): ≤ 4 % CV
• Use: Research use only
• Widely cited in over 70 publications

 

2.  MEASUREMENT OF BIOLOGICAL PEROXIDES 

Oxidative Stress Test – OXYSTAT Assay | BI-5007

Quick and easy assay to measure total peroxides in biological fluids.

• Method: colorimetric assay, 96 wells
• Sample type: serum, plasma, biological fluids
• Sample volume 10µl/well
• Assay time: 15 min
• Detection range: 0 – 660 µmol/l
• Sensitivity: 7 µmol/l
• Use: Research use only
• Widely cited in over 50 publications

 

Results show a direct correlation between free radicals and circulating biological peroxides and thus allow the characterization of the oxidative status in biological samples.

Literature

1. WHO-international health topics-cardiovascular diseases.
2. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Taniyama Y, Griendling KK. Hypertension. 2003 Dec;42(6):1075-81. doi: 10.1161/01.HYP.0000100443.09293.4F. Epub 2003 Oct 27. PMID: 14581295.
3. Atherosclerosis: process, indicators, risk factors and new hopes. Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Int J Prev Med. 2014 Aug;5(8):927-46. PMID: 25489440; PMCID: PMC4258672.
4. Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy. Hartley A, Haskard D, Khamis R. Trends Cardiovasc Med. 2019 Jan;29(1):22-26. doi: 10.1016/j.tcm.2018.05.010. Epub 2018 Jun 4. PMID: 29934015.
5. How Oxidized Low-Density Lipoprotein Activates Inflammatory Responses. Rhoads JP, Major AS. Crit Rev Immunol. 2018;38(4):333-342. doi: 10.1615/CritRevImmunol.2018026483. PMID: 30806246; PMCID: PMC6527110.
6. Anti-Oxidized LDL Antibodies and Coronary Artery Disease: A Systematic Review. van den Berg VJ, Vroegindewey MM, Kardys I, Boersma E, Haskard D, Hartley A, Khamis R. Antioxidants (Basel). 2019 Oct 15;8(10):484. doi: 10.3390/antiox8100484. PMID: 31618991; PMCID: PMC6826549
7. Circulating oxidized low density lipoprotein, autoantibodies against them and homocysteine serum levels in diagnosis and estimation of severity of coronary artery disease. Faviou E, Vourli G, Nounopoulos C, Zachari A, Dionyssiou-Asteriou A. Free Radic Res. 2005 Apr;39(4):419-29. doi: 10.1080/10715760500072156. PMID: 16028367.
8. Antibodies to oxidized low-density lipoprotein in patients following coronary artery revascularization. Miller ER 3rd, Erlinger TP, Blumenthal RS, Margolis S, Allen JK. Coron Artery Dis. 2003 Apr;14(2):163-9. doi: 10.1097/00019501-200304000-00009. PMID: 12655280.