There exist two opposing perspectives regarding reactive oxygen species (ROS) and their roles in angiogenesis and cardiovascular system, one that favors harmful and causal effects of ROS, while the other supports beneficial effects. Recent studies have shown that interaction between ROS in different sub-cellular compartments plays a crucial role in determining the outcomes (beneficial vs. deleterious) of ROS exposures on the vascular system. Oxidant radicals in one cellular organelle can affect the ROS content and function in other sub-cellular compartments in endothelial cells (ECs). In this review, we will focus on a critical fact that the effects or the final phenotypic outcome of ROS exposure to EC are tissue- or organ-specific, and depend on the spatial (subcellular localization) and temporal (duration of ROS exposure) modulation of ROS levels.
Cardiovascular diseases (CVD) are one of the prime causes of mortality worldwide. Experimental animal models have become a valuable tool to investigate and further advance our knowledge on etiology, pathophysiology and intervention. They also provide a great opportunity to understand the contribution of different genes and effector molecules in the pathogenesis and development of diseases at the sub-cellular levels. High levels of reactive oxygen species (ROS) have been associated with the progression of CVD such as ischemic heart disease (IHD), myocardial infarction, hypertension, atherosclerosis, aortic aneurysm, aortic dissection and others. On the contrary, low levels of antioxidants were associated with exacerbated cardiovascular event. Major focus of this review is on vascular pathogenesis that leads to CVD, with special emphasis on the roles of oxidant/antioxidant enzymes in health and disease progression in vascular cells including vascular endothelium. The major oxidant enzymes that have been implicated with the progression of CVD include NADPH Oxidase, nitric oxide synthase, monoamine oxidase, and xanthine oxidoreductase. The major antioxidant enzymes that have been attributed to normalizing the levels of oxidative stress include superoxide dismutases, catalase and glutathione peroxidases (GPx), and thioredoxin. Cardiovascular phenotypes of major oxidants and antioxidants knockout and transgenic animal models are discussed here.
BackgroundLeft ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)?MethodsThis is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile.ResultsNinety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients.ConclusionIn our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.
For decades, elevated levels of reactive oxygen species (ROS) have been associated with the pathogenesis of cardiovascular diseases (CVD), including myocardial ischemia and infarction (MI). However, several large clinical trials failed to demonstrate beneficial outcomes in response to the global reduction of ROS in patients with underlying CVD. Recent studies from our and other labs showed that it is rather a critical balance between mitochondrial and cytosolic ROS than total ROS levels which determines resilience of coronary endothelial cells (EC). Here, we will discuss published and unpublished work that has helped elucidate the molecular mechanisms by which subcellular ROS levels, duration and localization modulate metabolic pathways, including glycolysis and oxidative phosphorylation, energy production and utilization, and dNTP synthesis in EC. These redox-regulated processes play critical roles in providing resilience to EC which in turn help protect existing coronary vessels and induce coronary angiogenesis to improve post-MI recovery of cardiac function.
Left ventricular pseudoaneurysm (LVPA) formation is a potentially lethal complication of myocardial infarction (MI] and mitral valve (MV) replacement that requires prompt diagnosis and treatment. A female patient who had been complaining of exertional dyspnea underwent a two-dimensional transthoracic echocardiogram (TTE) which revealed a functioning mechanical MV with severe paravalvular leak, severe tricuspid regurgitation (TR) and severely elevated pulmonary artery systolic pressure. Moreover, echo-lucent space at the postero-lateral portion of the left ventricle near the MV was seen, suggestive of a large LVPA. Transesophageal echocardiography (TEE) and Computed Tomography (CT) angiography confirmed these findings. Afterwards, the patient had a surgical repair for the LVPA along with mitral and tricuspid valve (TV) replacement. Three months later, the patient presented with symptoms of congestive heart failure. The LVPA had recurred at the same location of the previous pseudoaneurysm and given the high risk for reoperating on the patient, close monitoring and medical management was deemed as a better option.
Background:
The use of complementary and alternative medicines (CAMs) has been embedded in populations for decades. In this study, we aimed to determine the rate of their usage among inflammatory bowel disease (IBD) patients and their association with adherence to conventional therapies.
Methods:
In this cross sectional, survey-based study, IBD patients’ (n=226) adherence and compliance were evaluated using the Morisky Medication Adherence Scale-8. A control sample of 227 patients with other gastrointestinal diseases was included to compare trends of CAM use.
Results:
Crohn’s disease represented 66.4% of those with IBD, with a mean age of 35 ± 13.0 years (54% males). The control group had either chronic viral hepatitis B, gastroesophageal reflux disease, Celiac disease, or other non-IBD diseases, with a mean age of 43.5 ± 16.8 years (55% males). Overall, 49% of patients reported using CAMs (54% in IBD group and 43% in the non-IBD group, P =0.024). Across both groups, the most used CAMs were honey (28%) and Zamzam water (19%). There was no significant association between the severity of the illness and use of CAMs. Patients who used CAMs had a lower adherence to conventional therapies vs. those who did not use CAMs (39% vs. 23%, P =0.038). Using the Morisky Medication Adherence Scale-8, low adherence to medications was reported in 35% of the IBD group vs. 11% of non-IBD group (P = 0.01).
Conclusion:
In our population, patients with IBD are more likely to use CAMs and are less adherent to medications. Furthermore, the use of CAMs was associated with a lower adherence rate to conventional therapies. Consequently, further studies assessing the causes associated with the use of CAMs and nonadherence to conventional therapies should be explored and interventions designed to mitigate nonadherence.
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