Biomedical subjects
Publications and source records attributed to A M Zafari.
Myocardial ischaemia during exercise electrocardiography is usually manifested by ST segment depression or elevation. Transient abnormal Q waves are rare, as Q waves indicate an old myocardial infarction. The case of a patient with exercise induced transient abnormal Q waves is reported. The potential mechanisms involved in the development of such an abnormality and its clinical implications are discussed.
Groin complications after cardiac catheterizations are common. With the increasing use of mechanical hemostatic devices, cardiologists must be alert to a wide array of potential problems. We report an unusual complication after the use of a closure device.
Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic acid metabolism is blocked with 5,8,11,14-eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 +/- 10%. In VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent superoxide production. In these cells, or in cells in which NADH/NADPH oxidase activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine incorporation is also inhibited. Attenuation of oxidase activation by inhibiting arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits angiotensin II-stimulated protein synthesis (74 +/- 2% and 34 +/- 1%, respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites mediate angiotensin II-stimulated protein synthesis in cultured VSMC by activating the NADH/NADPH oxidase, providing mechanistic evidence for redox control of VSMC hypertrophy.
Despite the significant reduction in cardiovascular mortality during the past three decades, atherosclerotic coronary heart disease (CHD) remains the leading cause of death and disability in the United States. Randomized clinical trials in patients with CHD have provided convincing evidence that risk factor modification is beneficial in decreasing all-cause mortality and cardiovascular morbidity and mortality. Multifactorial coronary risk reduction provides the most substantial benefit. Coronary risk reduction is associated with a decrease in cardiovascular-related hospital admissions, a reduced need for myocardial revascularization procedures, and an improved quality of life for the patients so treated. Control of coronary risk factors is an integral component of the optimal care of the patient with CHD.
Recent evidence suggests that oxidative mechanisms may be involved in vascular smooth muscle cell (VSMC) hypertrophy. We previously showed that angiotensin II (Ang II) increases superoxide production by activating an NADH/NADPH oxidase, which contributes to hypertrophy. In this study, we determined whether Ang II stimulation of this oxidase results in H2O2 production by studying the effects of Ang II on intracellular H2O2 generation, intracellular superoxide dismutase and catalase activity, and hypertrophy. Ang II (100 nmol/L) significantly increased intracellular H2O2 levels at 4 hours. Neither superoxide dismutase activity nor catalase activity was affected by Ang II; the SOD present in VSMCs is sufficient to metabolize Ang II-stimulated superoxide to H2O2, which accumulates more rapidly than it is degraded by catalase. This increase in H2O2 was inhibited by extracellular catalase, diphenylene iodonium, an inhibitor of the NADH/NADPH oxidase, and the AT1 receptor blocker losartan. In VSMCs stably transfected with antisense p22phox, a critical component of the NADH/NADPH oxidase in which oxidase activity was markedly reduced, Ang II-induced production of H2O2 was almost completely inhibited, confirming that the source of Ang II-induced H2O2 was the NADH/NADPH oxidase. Using a novel cell line that stably overexpresses catalase, we showed that this increased H2O2 is a critical step in VSMC hypertrophy, a hallmark of many vascular diseases. Inhibition of intracellular superoxide dismutase by diethylthiocarbamate (1 mmol/L) also resulted in attenuation of Ang II-induced hypertrophy (62+/-2% inhibition). These data indicate that AT1 receptor-mediated production of superoxide generated by the NADH/NADPH oxidase is followed by an increase in intracellular H2O2, suggesting a specific role for these oxygen species and scavenging systems in modifying the intracellular redox state in vascular growth.
Superoxide anion formation is vital to the microbicidal activity of phagocytes. Recently, however, there is accumulating evidence that it is also involved in cell growth in vascular smooth muscle cells (VSMCs). We have shown that the hypertrophic agent angiotensin II stimulates superoxide production by activating the membrane-bound NADH/NADPH oxidase and that inhibition of this oxidase attenuates vascular hypertrophy. However, the molecular identity of this oxidase in VSMCs is unknown. We have recently cloned the cytochrome b558 alpha-subunit, p22(phox) (one of the key electron transfer elements of the NADPH oxidase in phagocytes), from a rat VSMC cDNA library, but its role in VSMC oxidase activity remains unclarified. Here we report that the complete inhibition of p22(phox) mRNA expression by stable transfection of antisense p22(phox) cDNA into VSMCs results in a decrease in cytochrome b content, which is accompanied by a significant inhibition of angiotensin II-stimulated NADH/NADPH-dependent superoxide production, subsequent hydrogen peroxide production, and [3H]leucine incorporation. We provide the first evidence that p22(phox) is a critical component of superoxide-generating vascular NADH/NADPH oxidase and suggest a central role for this oxidase system in vascular hypertrophy.
OBJECTIVES: This study evaluated morphologic features of fossa ovalis membrane aneurysm and associated cardiac abnormalities that may predispose to systemic embolism. BACKGROUND: An increasing number of fossa ovalis membrane aneurysms are diagnosed by echocardiography. Higher frequencies of such aneurysms have been reported in patients with embolic stroke. METHODS: The hearts of 20 adults with fossa ovalis membrane aneurysms (mean [ +/- SD] age 62 +/- 19 years, range 24 to 87; 12 women [60%], 8 men [40%]) were examined. The areas of excised atrial septum, fossa ovalis membrane and fossa ovalis were measured. An aneurysm was defined as the ratio of the fossa ovalis membrane to fossa ovalis area > or = 1.5. RESULTS: Compared with a control group of 20 adults (mean age 58 +/- 21 years, range 18 to 86; 12 women [60%], 8 men [40%]), the 20 patients with fossa ovalis membrane aneurysm had larger (711 +/- 240 vs. 203 +/- 105 mm2, p < 0.0001) and thinner fossa ovalis membranes (0.6 +/- 0.1 vs. 1.9 +/- 0.9 mm2, p < 0.0001). The mean ratio of the fossa ovalis membrane to fossa ovalis area was 2.1 +/- 0.4 in patients with and 1.2 +/- 0.1 in those without fossa ovalis membrane aneurysm. Patent foramen ovale was seen in 14 (70%) of 20 patients with fossa ovalis membrane aneurysm and in 4 (20%) of 20 control subjects (p = 0.0005). CONCLUSIONS: Fossa ovalis membrane aneurysm is characterized by thinning and marked redundancy without adherent thrombi or fibrin tags. Mitral valve prolapse, dilated atria, intracardiac thrombi and patent foramen ovale are frequently seen in association with fossa ovalis membrane aneurysm and may explain the increased frequency of embolic stroke in patients with such aneurysms.
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