Elevated troponin and jarisch-herxheimer reaction in tick-borne relapsing Fever: a case report.

We describe a patient with fever and borreliosis in the Northwestern Washington State, USA. The patient exhibited a classic Jarisch-Herxheimer reaction of tachycardia, hypotension, and thrombocytopenia following antimicrobial therapy, and she also developed an elevated serum cardiac troponin during therapy.

Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail.

Oxidative stress and increased oxidation of low-density lipoprotein (oxLDL) through free radical-mediated tissue injury may be important factors in the development of extracranial atherosclerotic lesions. However, the roles of oxidative stress and hypercholesterolemia in intracranial atherosclerosis is less established. The induction of heme oxygenase (HO) is a cellular response to oxidative stress, and inducible HO (HO-1) may protect against oxidized lipids such as those produced by oxidative stress. We investigated the effects of oxLDL on cell and tissue viability, HO-1 and ferritin expression in extracranial and intracranial endothelial cells, and the arteries of cholesterol-induced atherosclerosis (CIA) Japanese quail. We report that cultured microvascular endothelial cells from the brain (QBMEC) and carotid (QCEC) differ in their response to oxidative stress. The QCECs are less responsive than QBMECs to oxidative stress induced by oxLDL, as evident by lower expression of HO-1 mRNA, HO activity, and ferritin levels. Furthermore, the higher levels of catalytic iron, thiobarbituric acid reactive substances, and lactate dehydrogenase released in QCECs indicated that these cells are more susceptible to oxidative stress than QBMECs. We also investigated the relationship between extent of atherosclerotic plaque deposition and the extracranial and intracranial arterial expression of HO-1 in quail. The common carotid and vertebral (extracranial) arteries had higher tissue cholesterol levels (starting at 2 weeks of cholesterol-supplementation) and a greater atherosclerotic plaque score (starting at 4 weeks of cholesterol-supplementation) compared with middle cerebral and basilar (intracranial) arteries, and this may be relevant to the effect of aging on the process of atherogenesis. The extracranial arteries also had early and greater levels of lipid peroxidation and catalytic iron coupled with lower expression of HO-1 protein, HO activity, and ferritin compared to the intracranial vessels. These observations suggest that the extracranial and intracranial arterial walls respond differently to oxidation of lipoproteins, and support the feasibility of increased HO-1 expression as a means of protection against oxidant injury.

Protective role of heme oxygenase in the blood vessel wall during atherogenesis.

Several lines of evidence suggest that antioxidant processes and (or) endogenous antioxidants inhibit proatherogenic events in the blood vessel wall. Heme oxygenase (HO), which catabolizes heme to biliverdin, carbon monoxide, and catalytic iron, has been shown to have such antioxidative properties. The HO-1 isoform of heme oxygenase is ubiquitous and can be increased several fold by stimuli that induce cellular oxidative stress. Products of the HO reaction have important effects: carbon monoxide is a potent vasodilator, which is thought to play a role in modulation of vascular tone; biliverdin and its by-product bilirubin are potent antioxidants. Although HO induction results in an increase in catalytic free iron release, the enhancement of intracellular ferritin protein through HO-1 has been reported to decrease the cytotoxic effects of iron. Oxidized LDL has been shown to increase HO-1 expression in endothelial and smooth muscle cell cultures, and during atherogenesis. Further evidence of HO-1 expression associated with atherogenesis has been demonstrated in human, murine and rabbit atherosclerotic lesions. Moreover, genetic models of HO deficiency suggest that the actions of HO-1 are important in modulating the severity of atherosclerosis. Recent experiments in gene therapy using the HO gene suggest that interventions aimed at HO in the vessel wall could provide a novel therapeutic approach for the treatment or prevention of atherosclerotic disease.

Effects of oxidant-induced injury on heme oxygenase and glutathione in cultured aortic endothelial cells from atherosclerosis-susceptible and -resistant Japanese quail.

Recent studies on cultured aortic endothelial cells (AECs) from atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail suggest that differences in atherosclerosis susceptibility between RES and SUS may be due to differences in endothelial heme oxygenase (HO) and antioxidant components. We have now investigated the effects of oxidant-induced injury on HO and glutathione (GSH) in AECs from SUS and RES quail. We report that cultured AECs from SUS and RES birds differ in their response to oxidative stress. AECs from the SUS strain cells are more susceptible than those from the RES strain to oxidative stress induced by tert-butylhydroperoxide, as judged by lower HO activity, HO-1 expression, ferritin and GSH levels. Aortic endothelial cells from SUS birds also showed higher levels of catalytic iron, TBARS production and LDH release compared with RES cells, indicating that SUS AECs are more susceptible to oxidative stress than cells from the resistant strain. Furthermore, independently of genetic status, AECs from old birds have higher TBARS and lower levels of HSP70 induction than AECs from younger birds, suggesting that aging is associated with a decreased ability of AECs to respond to oxidative stress, and this may be relevant to the permissive effect of aging on the process of atherogenesis. Our results indicate that genetic factors and endogenous antioxidant systems in the blood vessel wall may be important in determining the susceptibility of vascular cells to oxidative stress and atherosclerotic plaque formation.

Alterations in aortic antioxidant components in an experimental model of atherosclerosis: a time-course study.

Antioxidant component alterations in the aorta during atherogenesis were examined in atherosclerosis-susceptible (SUS) Japanese quail fed a cholesterol-supplemented (0.5% w/w) diet. Birds fed a non-supplemented diet provided information on the effects of aging on endogenous antioxidants. One hundred adult SUS males were used. Birds were sacrificed after 0, 4, 8 and 12 weeks on the diets and were examined for plaque development and corresponding antioxidant component alterations in aorta and myocardium. With aging, superoxide dismutase (SOD) activity was increased in both tissues, whereas aortic glutathione peroxidase (GPx) activity and myocardial glutathione reductase (GRd) activity decreased. Myocardial ascorbate levels increased with aging, with a reciprocal decrease in myocardial tocopherol levels. Following 4 weeks of cholesterol supplementation, aortic GRd decreased, SOD activity increased, but activities of GPx and catalase were unchanged. This same qualitative pattern of antioxidant enzyme changes was also found in myocardium. Thus, although aortic antioxidant enzyme changes produced by cholesterol feeding and aging showed some similarities, the early phase of atherogenesis does not simply reflect accelerated aging. In the late stages of atherogenesis, SOD activity returned to baseline, but other antioxidant enzymes remained unaltered from levels characterizing the early phase of lesion development. There was no detectable functional coupling between changes in GPx and GRd, nor between SOD (which produces hydrogen peroxide) and GPx or catalase (which utilize hydrogen peroxide as substrate). Previously reported alterations in erythrocyte antioxidant enzyme components during atherogenesis in quail were not predictive of changes in the corresponding enzymes in the aorta and myocardium.

Heme oxygenase and antioxidant status in cultured aortic endothelial cells isolated from atherosclerosis-susceptible and -resistant Japanese quail.

We have investigated heme oxygenase (HO) and antioxidant status in the novel isolation and characterization of aortic endothelial cells (AECs) from a random bred wild-type strain (WILD) and selectively bred atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail. Cultured AECs expressed acetylated LDL, and were probed with endothelial and smooth muscle cell specific antibodies to confirm purity of culture. Subconfluent monolayers of RES AECs had higher HO activity than SUS AECs. At confluence, HO activity levels were similar among strains. However, RES AECs had higher HO-1 protein than WILD and SUS cells. Although ferritin protein levels were similar among the three strains, catalytic iron was higher in SUS AECs than WILD and RES cells. Glutathione levels were highest in SUS cells, intermediate in WILD, and lowest in RES, while glutathione reductase was higher in WILD and RES AECs than SUS AECs. We suggest that differences in atherosclerosis susceptibility between RES and SUS may be due, at least in part, to differences in endothelial HO and antioxidant components.