Proteomic analysis of hypothalamic injury in heatstroke rats.

Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms.

Attenuating systemic inflammatory markers in simulated high-altitude exposure by heat shock protein 70-mediated hypobaric hypoxia preconditioning in rats.

BACKGROUND/PURPOSE: The primary goal of this study was to test whether high-altitude exposure (HAE: 0.9% O(2) at 0.47 ATA for 24 hours) was capable of increasing the systemic inflammatory markers as well as the toxic organ injury indicators in rats, with a secondary goal to test whether preinduction of heat shock protein (HSP) 70 by hypobaric hypoxia preconditioning (HHP: 18.3% O(2) at 0.66 ATA for 5 h/day on 5 days consecutively for 2 weeks) attenuated the proposed increased serum levels of both the systemic inflammatory markers and the toxic organ injury indicators. METHODS: Rats were assigned to: (1) non-HHP (21% O(2) at 1.0 ATA)+non-HAE (21% O(2) at 1.0 ATA) group; (2) non-HHP+HAE group; (3) HHP+non-HAE group; (4) HHP+HAE group; and (5) HHP+HSP70 antibodies (Ab)+HAE group. For the HSP70Ab group, a neutralizing HSP70Ab was injected intravenously at 24 hours prior to HAE. All the physiological and biochemical parameters were obtained at the end of HAE or the equivalent time period of non-HAE. Blood samples were obtained for determination of both the systemic inflammatory markers (e.g., serum tumor necrosis factor-α, interleukin-1ß, E-selectin, intercellular adhesion molecule-1, and liver myeloperoxidase activity) and the toxic organ injury indicators (e.g., nitric oxide metabolites, 2,3-dihydroxybenzoic acid, and lactate dehydrogenase). RESULTS: HHP, in addition to inducing overexpression of tissue HSP70, significantly attenuated the HAE-induced hypotension, bradycardia, hypoxia, acidosis, and increased tissue levels of both the systemic inflammatory markers and the toxic organ injury indicators. The beneficial effects of HHP in inducing tissue overexpression of HSP70 as well as in preventing the HAE-induced increased levels of the systemic inflammatory markers and the toxic organ injury indicators could be significantly reduced by HSP70Ab preconditioning. CONCLUSION: These results suggest that HHP may downgrade both the systemic inflammatory markers and the toxic organ injury indicators in HAE by upregulating tissue HSP70.

Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70.

Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways.

Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-α antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-α. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-α expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-α was measured by Immunofluorescence staining. In addition, TNFα contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: In addition to inducing brain ischemia as well as neurological and motor deficits, TBI caused significantly higher numbers of microglia-TNF-α double positive cells, but not neurons-TNF-α or astrocytes-TNF-α double positive cells in the injured brain areas than did the sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral ischemia, neurological motor deficits, and increased numbers of microglia-TNF-α double positive cells and increased TNF-α levels in the injured brain were all significantly attenuated by etanercept therapy. CONCLUSION: This finding indicates that early microglia overproduction of TNF-α in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.

Attenuating heat-induced cellular autophagy, apoptosis and damage in H9c2 cardiomyocytes by pre-inducing HSP70 with heat shock preconditioning.

PURPOSE: We sought to assess whether heat-induced autophagy, apoptosis and cell damage in H9c2 cells can be affected by pre-inducing HSP70 (heat shock protein 70). MATERIALS AND METHODS: Cell viability was determined using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide staining and a lactate dehydrogenase assay. Apoptosis was evidenced using both flow cytometry and counting caspase-3 positive cells, whereas autophagy was evidenced by the increased LC3-II expression and lysosomal activity. RESULTS: The viability of H9c2 cells was temperature-dependently (40-44 °C) and time-dependently (90-180 min) significantly (p < 0.05) reduced by severe heat, which caused cell damage, apoptosis and autophagy. Heat-induced cell injury could be attenuated by pretreatment with 3-methylademine (an autophagy inhibitor) or Z-DEVD-FMK (a caspase-3 inhibitor). Neither apoptosis nor autophagy over the levels found in normothermic controls was induced in heat-shock preconditioned controls (no subsequent heat injury). The beneficial effects of mild heat preconditioning (preventing heat-induced cell damage, apoptosis and autophagy) were significantly attenuated by inhibiting HSP70 overexpression with triptolide (Tripterygium wilfordii) pretreatment. CONCLUSION: We conclude that pre-inducing HSP70 attenuates heat-stimulated cell autophagy, apoptosis and damage in the heart. However, this requires in vivo confirmation.

Etanercept attenuates traumatic brain injury in rats by reducing brain TNF- α contents and by stimulating newly formed neurogenesis.

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF- α and/or stimulating newly formed neurogenesis. Rats that sustained TBI are immediately treated with etanercept. Acute neurological and motor injury is assessed in all rats the day prior to and 7 days after surgery. The numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain injury that occurred during TBI were counted by immunofluorescence staining. Enzyme immunoassay for quantitative determination of TNF-α or etanercept in brain tissues is also performed. Seven days after systemic administration of etanercept, levels of etanercept can be detected in the contused brain tissues. In addition, neurological and motor deficits, cerebral contusion, and increased brain TNF-α contents caused by TBI can be attenuated by etanercept therapy. Furthermore, the increased numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain tissues caused by TBI can be potentiated by etanercept therapy. These findings indicate that systemically administered etanercept may penetrate directly into the contused brain tissues and may improve outcomes of TBI by reducing brain contents of TNF- α and by stimulating newly formed neurogenesis.

Robot-assisted endoscopic removal of a huge tricuspid valve myxoma: case report.

BACKGROUND: Cardiac myxoma is the most common benign cardiac tumor. Its tremendous size and fragile character severely bother the surgeons. Several minimal invasive approaches had been applied for radical tumor excision. The wound was forcibly enlarged for en-bloc specimen removal and prevention of debris sputtering. CASE PRESENTATION: We reported a case of huge tricuspid valve (TV) myxoma managed by robot-assisted endoscopic tumor resection and TV repair, with initial presentation of worsening shortness of breath for two months. The tumor was downsized with a morcellator and removed through a keyhole wound (1.1 cm in diameter). The patient recovered uneventfully and was discharged after four days. CONCLUSIONS: With the first morcellator application, this might be the smallest surgical wound reported after the removal of a huge cardiac myxoma. The ICU and hospital stays were shortened. This might be effectively applied to further minimally invasive surgeries for cardiac tumor excision.

Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation-Induced Myocardial Dysfunction.

Background Mitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR-induced HF. Methods and Results Using a novel, mini-invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR-induced impairment including partial restoration of left ventricular ejection fraction and end-systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing-induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress-associated proteins. Conclusions DAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR-induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio-protective function, provides a plausible point of DAPA as a potential strategy for MR-induced HF.

Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization.

Right ventricular impairment is a predictor of cardiovascular outcomes in patients with degenerative mitral regurgitation. However, the time course of right ventricular functional changes post-surgical mitral valve repair remains largely unknown. Herein, using right ventricular-focused echocardiography, we aimed to investigate right ventricular reserve and its impact on hospitalization for heart failure after mitral valve repair. In this prospective study, we enrolled 108 patients scheduled to undergo surgical repair of degenerative mitral regurgitation. Echocardiography, including right ventricular strain analysis, was performed prior to, and one month and six months post mitral valve repair. Right ventricular strain that improved one month post-surgery was defined as reserved right ventricular. In addition, any cardiovascular outcomes comprising heart failure that required admission were recorded. The median follow-up duration is 31 months. Despite a significant improvement in mitral valve regurgitant volume post-operatively, left ventricular ejection fraction (LVEF) at six months was similar to LVEF at baseline. There was a transient decrease in LV longitudinal strain at one month that was recovered six months post mitral valve repair. Regarding the right ventricular, in contrast with conventional right ventricular parameters, including right ventricular tissue Doppler S', fractional area change and tricuspid annular plane systolic excursion (TAPSE), only resolution of right ventricular strain at one month predicted the subsequent myocardial recovery. Furthermore, patients with reserved right ventricular had a lower risk of hospitalization for heart failure compared to those with non-reserved right ventricular. Collectively, the early resolution of right ventricular strain is associated with the improvement in right ventricular function (measured by TAPSE) and in heart failure hospitalization in patients who had undergone surgical mitral valve repair for degenerative mitral regurgitation.

Influence of warfarin on cardiac and cerebrovascular events following bioprosthetic aortic valve replacement: A nationwide cohort study.

OBJECTIVE: The need for anticoagulation treatment following bioprosthetic aortic valve replacement remains controversial. We investigated the associations of warfarin treatment with the risks of major adverse cardiac and cerebrovascular events, including mortality, bleeding incidents, and reoperation requirement after bioprosthetic aortic valve replacement surgery. METHODS: We identified 1086 patients who received first bioprosthetic aortic valve replacement between 2001 and 2010 using Taiwan's National Health Insurance Database. Patients were excluded for prior use of warfarin, warfarin use for >3 months, dual valve procedures, prior valve surgeries, or concomitant surgeries. Enrolled patients were divided into 2 groups according to whether they were warfarin-naïve or received warfarin for <3 months postsurgery. After propensity score matching, 282 patients not receiving warfarin were matched to 282 patients receiving warfarin for <3 months. Patients were followed-up for minimum 36 months. RESULTS: Patients receiving warfarin were younger and showed less frequent kidney disease than those who did not use warfarin. The warfarin group demonstrated a gross decrease in major adverse cardiac and cerebrovascular events. Patients receiving warfarin for <30 days were at an even lower risk for major adverse cardiac and cerebrovascular events than those treated for ≥30 days. No significant difference in bleeding or reoperation risk was observed between warfarin users and warfarin nonusers. Similar findings remained after propensity-score matching but the benefit of short-term warfarin use diminished in a younger population. CONCLUSIONS: Short-term use of postoperative warfarin (especially <30 days) following bioprosthetic aortic valve replacement may be associated with a reduction in MACCE compared with nonuse.

Small volume resuscitation in a rat model of heatstroke.

BACKGROUND: Herein, we compared the effectiveness of different small volume resuscitation in a rat model of heatstroke. METHODS: Anesthetized rats, immediately after the onset of heatstroke, were randomly divided into 5 groups and given the following: (a) nothing; (b) 0.9% NaCl (1-10 mL/kg of body weight, i.v.); (c) hydroxyethyl starch (HAES) (6%, 1-10 mL/kg of body weight, i.v.); (d) 7.2% NaCl (1-10 mL/kg of body weight, i.v.); and (e) hyper-HAES (6% HAES plus 7.2% NaCl, 1-10 mL/kg of body weight, i.v.). RESULTS: When the untreated or 0.9% NaCl (1-5 mL/kg of body weight)-treated rats underwent heat stress, their survival time values were found to be 20 to 22 minutes. Resuscitation with 10 mL/kg of body weight of 0.9% NaCl, 6% HAES, 7.2% NaCl, or hyper-HAES, their survival time values, respectively, are 93+/-6, 101+/-12, 154+/-18, or 286+/-21. Apparently, the order of effectiveness in resuscitation of heatstroke is hyper-HAES>7.2% NaCl>0.9% NaCl or 6% HAES. The heatstroke-induced hypotension, cerebral ischemia and hypoxia, hypercoagulable state, activated inflammation, and hepatic and renal dysfunction can be significantly reduced by hyper-HAES. CONCLUSIONS: Our results suggest that hyper-HAES seems superior to 7.2% NaCl or HAES alone in resuscitation of heatstroke. The benefit of hyper-HAES during heatstroke is related to restoration of normal multiorgan function.

Transcatheter atrioventricular valve-in-valve implantation for Fontan circulation and dextrocardia.

Transcatheter heart valve-in-valve implantation in failed surgical bioprosthetic valves has shown promising outcomes, prompting the stepwise expansion of their applications in different clinical scenarios. Recently, there is increased interest in valve-in-valve techniques for the treatment of patients with complex congenital heart disease. Herein, we report a case of successful transapical transcatheter atrioventricular valve-in-valve implantation in a patient with Fontan circulation and dextrocardia. The patient was previously treated with total cavopulmonary connection and atrioventricular valve replacement with recurrent prosthesis dysfunction.

Both mild hypothermia and dopamine D(2) agonist are neuroprotective against hyperthermia-induced injury in PC12 cells.

We exposed rat pheochromocytoma PC12 cells to hyperthermia or high dosage of dopamine and examined the direct effects of mild hypothermia or dopamine D(2) receptor agonist. At a hyperthermia of 42-43 degrees C for 120 min there was approximately 50% loss of cell viability accompanied by dopamine overproduction. The model of cell death due to hyperthermia in PC12 cells belonged to the necrotic and late apoptotic population. At each temperature examined below 37 degrees C, significant decrease in cytotoxicity, the percentage of necrotic and late apoptotic cells, and dopamine overproduction were observed. Cytotoxicity could also be induced by high dosages of dopamine. Both hyperthermia and dopamine induced cytotoxicity in PC12 cells could also be reduced by dopamine D(2) agonists. These results indicate the dopamine is important in hyperthermic situations. The results also indicate that mild hypothermia and dopamine D(2) receptor agonists are neuroprotective against hyperthermia-induced brain injury.

Robotic mitral valve replacements with bioprosthetic valves in 52 patients: experience from a tertiary referral hospital.

OBJECTIVES: Robotic mitral valve replacement (MVR) emerged in the late 1990s as an alternative approach to conventional sternotomy. With the increased use of bioprosthetic valves worldwide and strong patient desire for minimally invasive procedures, the safety and feasibility of robotic MVRs with bioprosthetic valves require investigation. METHODS: Between January 2013 and May 2017, 52 consecutive patients underwent robotic MVRs using the da Vinci Si surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA). Their mean age was 55.1 ± 13.8 years, and mean EuroSCORE II was 2.25% ± 1.25%. Among the enrolled patients, 32 (61.5%) patients presented with preoperative atrial fibrillation, 6 (11.5%) patients had experienced embolic stroke and 5 (9.6%) patients had undergone previous cardiac surgery. The operations were performed using cardiopulmonary bypass (CPB) under an arrested heart status. RESULTS: Five porcine valves and 47 bovine valves were implanted. A total of 38 (73.1%) patients received concomitant cardiac procedures, including 26 Cox-maze IV procedures, 12 tricuspid valve repairs and 5 atrial septal defect repairs. The mean aortic cross-clamp and CPB times were 141.3 ± 34.3 min and 217.1 ± 42.0 min, respectively. There was no operative mortality. During the mean follow-up of 29 ± 15 months, no prosthesis degeneration was noted. The average left atrial dimension exhibited a significant decrease from 51.4 ± 11.5 mm to 42.6 ± 10.1 mm. CONCLUSIONS: Robotic MVR with bioprosthetic valves is safe, feasible and reproducible. Mid-term results are encouraging. Both aortic cross-clamp and CPB times can be improved with experience.

Inhibition of neuronal nitric oxide synthase causes attenuation of cerebrovascular dysfunction in experimental heatstroke.

The present study was performed to assess the prophylactic effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1 mL per kg body weight) or 7-NI (5-20mg/mL per kg body weight) intraperitoneally. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 21-25 min. Pretreatment with intraperitoneal doses of 7-NI significantly improved survival during heatstroke (55-164 min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, neuronal damage score and nNOS expression in the hypothalamus, and tumor necrosis factor-alpha (TNF-alpha) in the serum. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of 7-NI before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, nNOS-dependent NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and neuronal damage score in the hypothalamus, as well as overproduction of TNF-alpha in the serum that occurred during heatstroke. The data show that reduction of nNOS-dependent NO(2)(-) with 7-NI causes attenuation of cerebrovascular dysfunction, hyperthermia, and TNF-alpha overproduction during heatstroke in the rat.

The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke.

The present study was performed to assess the prophylactic effect of baicalin, a flavonoid compound, in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1mL per kg body weight) or baicalin (10-40mg per kg body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 20-28min. Pretreatment with intravenous doses of baicalin significantly improved survival during heatstroke (65-248min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, and dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and hypothalamic levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as plasma levels of creatinine, serum urea nitrogen, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were elevated after heatstroke onset. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of baicalin before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, and the increased levels of NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and DHBA in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in both the serum and hypothalamus, and renal and hepatic dysfunction were suppressed by baicalin pretreatment. In contrast, both the serum and hypothalamic levels of IL-10 were significantly elevated by baicalin during heatstroke. We successfully demonstrated that baicalin can be used as a prophylactic agent for heatstroke. In particular, baicalin may protect against cerebrovascular dysfunction and brain inflammation in heatstroke.

IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis. METHODS AND RESULTS: We examined the expression of IL-20 and its receptor complex IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using immunohistochemical staining. IL-20 was expressed in macrophage-rich areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial cells lining the intimal microvessels, vasa vasorum, but rarely in nonatherosclerotic arteries. We used reverse-transcription polymerase chain reaction to analyze gene expression. IL-20 transcripts increased in hypoxic monocytes and monocytes treated with oxidized low-density lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated by human umbilical vein endothelial cells in response to hypoxic treatment. Incubating IL-20 with human umbilical vein endothelial cells upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo administration of IL-20 expression vector using intramuscular electroporation promoted atherosclerosis in apolipoprotein E-deficient mice. CONCLUSIONS: Our data suggest that IL-20 is a proatherogenic cytokine that contributes to the progression of atherosclerosis.