Research Area

Oxidative Stress and Cardiovascular


Introduction of oxidative Stress

Oxidative stress reflects the balance of the production of reactive oxygen species in living organisms and the neutralization of oxidized substances and repairing oxidative damage in biological systems is broken. When the normal redox state of the cells is disturbed, and the cells will produce peroxides and free radicals, which damage the components of the cells, including proteins, lipids and DNA. Oxidative stresses come from oxidative metabolism, it will cause basic damage and DNA strand breaks. The basic damage is caused indirectly by O2-, OH and H2O2 produced by reactive oxygen species (ROS). In clinical studies, oxidative stress is thought to be involved in the development of ADHD, cancer, Parkinson's disease, Lafora disease, Alzheimer's disease, atherosclerosis, heart failure, myocardial infarction, fragile X syndrome, sickle-cell disease, lichen planus, vitiligo, autism, infection, chronic Fatigue syndrome, and depression. However, ROS is not always harmful for body. It is necessary for some pathway, such as ROS acts as a cellular messenger to activate the redox signaling pathway; it can be used by the immune system as a way to kill pathogens. In addition, studies have shown that short-term oxidative stress is important for anti-aging function of mitohormesis.

Oxidative pressure is associated with an increase in oxidative species and a significant decrease in antioxidant defenses, and the effects of oxidative stress are dependent on these changes. Under normal physiological conditions, cells have the ability to overcome minor disturbances and return them to normal states. If cells suffer severe oxidative stress, the oxidative stress can cause cell death. In these processes, moderate oxidative stress can induce apoptosis, and strong oxidative stress can cause cell necrosis. The production of reactive oxygen species is the destructive side of oxidative stress. Some of the reactive oxygen species (such as less reactive superoxides) can be converted to more active free radical species by redox reactions and transition metal or other redox cycle compounds, which lead to more cells damage.

Oxidative Stress and Cardiovascular

The relationship between oxidative stress and cardiovascular

Vascular endothelial cells are single-layered squamous epitheliums that line the inner surface of the heart, blood vessels and lymphatic vessels. They form the inner wall of the blood vessel and have a semi-permeable membrane property. They can selectively allow certain substances in the blood to enter the blood vessel wall and act as a barrier. At the same time, vascular endothelial cells also have important secretory functions, which are the largest endocrine and paracrine organs in the body. The secreted factors are involved in biological processes such as vasoconstriction and relaxation, vascular smooth muscle proliferation, inflammation and signal transduction. Among them, the secretory function of endothelial cells plays an important role in the regulation of blood pressure, which not only releases endothelium-derived relaxing factors, including nitric oxide (NO), prostacyclin, endothelium-derived hyperpolarizing factor, etc. In addition, it also produces endothelium derived contracting factor, such as angiotensin II (Ang II), ROS, endothelin 1 and so on. There is a delicate balance between contractile and relaxing factors released by endothelial cells, and any factor that affects this balance can lead to endothelial dysfunction, which can lead to abnormal blood pressure. Among them, oxidative stress is one of the factors affecting endothelial function.

ROS in oxygen free radicals are closely related to oxidative stress. Under physiological conditions, there is a dynamic balance between the production and elimination of oxygen free radicals; however, under certain pathological stimuli, the antioxidant defense system in the body is damaged and/or the oxygen radicals are excessively produced, resulting in the dynamic balance between the generation and elimination of oxygen free radicals is destroyed. When the rate of ROS removal is less than the rate of production, the imbalance between the production of oxygen free radicals and antioxidants in the body can cause endothelial cell dysfunction. On the one hand, hypertension itself can aggravate endothelial damage, on the other hand, endothelial dysfunction and dysregulation of contraction and relaxation factors will increase the production of oxidative stress molecules such as superoxide anion and peroxynitrite, and impair endothelium-dependent vasodilation. And then the blood pressure rises, which creates a vicious circle.

Fortunately, there are not only pro-oxidative systems in the body, but also antioxidant defense systems. Among them, the pro-oxidase system includes reduced nicotinamide adenine dinucleotide phosphate (NADPH), oxidase (NOX), xanthine oxidoreductase (XOR) and the like; the antioxidant enzyme system includes superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxide reductase (Prx), and catalase. Nitric oxide synthase (eNOS) plays a major role in the oxidation of anti-vascular wall. NO is a signal molecule of the peripheral and central nervous system. In addition to its anti-oxidative stress, inhibition of vascular smooth muscle proliferation, inhibition of leukocyte adhesion, and anti-platelet aggregation, NO also has the function of maintaining vascular tone in the cardiovascular system, so the insufficient of NO production will cause the increase of blood pressure. eNOS is a key enzyme for NO production. It has three types in the human body, namely endothelial, inducible and neurological, and the three plays an important role in development of cardiovascular diseases such as hypertension, atherosclerosis and myocardial infarction. Among them, eNOS is mainly distributed in vascular endothelial cells and cardiomyocytes, and plays an important role in the pathogenesis of hypertension.

In addition, studies have found that oxidative stress can also participate in the development and progression of ischemic cardiomyopathy (ICM) by different mechanisms such as damage to cell membrane, Ca2+ overload, promotion of apoptosis, production of inflammatory mediators, leukocyte adhesion and activation, and damage to vascular endothelial cells.

Clinical significance

Since the cause of cardiovascular disease involves oxidative stress, effective antioxidant therapy has broad application prospects in preventing and treating ROS damage to the body, maintaining the basic state of vascular tone, and maintaining normal blood pressure. And the experimental results show that vitamin C and vitamin E supplementation can improve oxidative stress damage in patients with essential hypertension, thereby lowering blood pressure. At present, most of the evidence related to cardiovascular and anti-oxidative stress therapy come from experimental research, clinical observation and epidemiological data, these results are not completely consistent. It is not yet to find out whether existing the effect of antioxidants have direct treatment for cardiovascular disease. Therefore, further research on the relationship between the two is necessary for clinical treatment.

References:

  1. Noh H, Ha H. Reactive oxygen species and oxidative stress. Contrib Nephrol. 2011, 170: 102-112.
  2. Lee J, et al. Altered nitric oxide system in cardiovascular and renal diseases. Chonnam Med J. 2016, 52(2):81-90.
  3. Tsutsui M, et al. Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. J Pharmacol Sci. 2015, 127(1): 42-52.
  4. Winterbourn C C. Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol. 2008, 4(5): 278-286.
  5. Chandra K, et al. Protection Against FCA Induced Oxidative Stress Induced DNA Damage as a Model of Arthritis and In vitro Anti-arthritic Potential of Costus speciosus Rhizome Extract. International Journal of Pharmacognosy and Phytochemical Research. 2015, 7 (2): 383–389.
  6. Helbock H J, et al. DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. Proc. Natl. Acad. Sci. U.S.A. 1998, 95 (1): 288–93.

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