Jong-Hau Hsu

Kaohsiung Medical University, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (48)140.44 Total impact

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    ABSTRACT: It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction due to its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, iv) attenuated LPS-induced hypotension and tachycardia by 21% and 23 %, respectively (p<0.05), improved myocardial dysfunction (LVSP: 33%; Max dp/dt: 20%; Min dp/dt: 33%, p<0.05), and prevented hepatic dysfunction (GOT: 81 vs. 593 IU/L; GPT: 15 vs. 136 IU/L, p<0.05) compared with LPS-treated rats at 4 h. HSC70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, p<0.05) and elevated LDH (1312 vs. 6301 IU/L, p<0.05). Furthermore, HSC70 decreased LPS-induced elevation of circulating TNF-α and NOx, and tissue expression of iNOS, COX-2, MMP-9 in the heart and liver. To investigate underlying mechanisms, we found that HSC70 attenuated LPS-induced nuclear translocation of NF-κB subunit p65 by blocking the phosphorylation of IκBα. Finally, we showed that HSC70 repressed the activation of MAPKs caused by LPS. These results demonstrate that in LPS-induced septic shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic and systemic derangements, with associated inhibition of pro-inflammatory mediators including TNF-α, NO, COX-2, MMP-9, through MAPK/NF-κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.
    Shock (Augusta, Ga.) 09/2014; · 2.87 Impact Factor
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    ABSTRACT: Lysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.
    BMC Complementary and Alternative Medicine 07/2014; 14(1):233. · 2.08 Impact Factor
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    ABSTRACT: Background Pneumonia is a life-threatening disease in children. With the current lack of universal diagnostic criteria, the diagnosis is usually made on clinical manifestations and findings from chest radiographs. Ultrasonography has recently been applied to the detection of pulmonary diseases. However, few data have been published showing its effectiveness in detecting pneumonia in children. The objective of this study was to determine the power of lung ultrasonography (LUS) for the diagnosis of pneumonia in children. Materials and methods This retrospective study was carried out by reviewing medical records. Patients admitted to a pediatric ward with a diagnosis of pneumonia from June 1, 2010 to December 31, 2012 were enrolled in this study. Personal information, laboratory data, characteristics on LUS scan, and the results of chest radiography and LUS were collected. We compared the detection rate of pneumonia by chest radiography and LUS. LUS scans were followed up in 23 patients during the progression of their disease. Results A total of 163 patients was enrolled. Chest radiography was able to detect pneumonia in 152 patients, whereas LUS detected pneumonia in 159 patients. In LUS, the positive rates of the comet-tail sign, air bronchograms, fluid bronchograms, vascular pattern within the consolidation, and pleural effusion were 50.9%, 93.7%, 20.1%, and 28.9%, respectively. During follow up, the average size of the pneumonia patch in 23 patients decreased from 10.9 ± 8.7 cm2 to 5.5 ± 8.2 cm2, and finally to 2 ± 1.9 cm2 on Day 1, Days 3–5 and Days 7–14, respectively. Conclusion LUS is a sensitive diagnostic tool with which to identify pneumonia in children. It is also useful in following up the progress of pneumonia. We suggest that LUS is a complementary tool to chest radiography in the diagnosis of pneumonia in children and that the follow up of pneumonia by LUS can reduce the exposure of children to ionizing radiation.
    Pediatrics & Neonatology. 01/2014;
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    ABSTRACT: Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.
    The American journal of Chinese medicine. 01/2014; 42(4):785-97.
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    Jong-Hau Hsu, Tai-Heng Chen, Yuh-Jyh Jong
    Pediatric Pulmonology 12/2013; · 2.38 Impact Factor
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    ABSTRACT: Pulmonary vascular remodeling, characterized by disordered proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a pathognomonic feature of pulmonary arterial hypertension. Thus, pharmacologic strategy targeting on anti-proliferation and anti-migration of PASMCs may have therapeutic implications for PAH. Here we investigated the effects and underlying mechanisms of B-type natriuretic peptide (BNP) on angiotensin II (Ang II)-induced proliferation and migration of PASMCs. Proliferation and migration of PASMCs cultured from Wistar rats were induced by Ang II, with or without BNP treatment. In addition, potential underlying mechanisms including cell cycle progression, Ca(2+) overload, reactive oxygen species (ROS) production, signal transduction of MAPK and Akt, and the cGMP/PKG pathway were examined. We found that BNP inhibited Ang II-induced PASMCs proliferation and migration dose dependently. BNP could also arrest the cell cycle progression in the G0 /G1 -phase. In addition, BNP attenuated intracellular calcium overload caused by Ang II. Moreover, Ang II-induced ROS production was mitigated by BNP, with associated down-regulation of NAD(P)H oxidase 1 (Nox1) and reduced mitochondrial ROS production. Finally, Ang II-activated MAPKs and Akt were also counteracted by BNP. Of note, all these effects of BNP were abolished by a PKG inhibitor (Rp-8-Br-PET-cGMPS). In conclusion, BNP inhibits Ang II-induced PASMCs proliferation and migration. These effects are potentially mediated by decreased calcium influx, reduced ROS production by Nox1 and mitochondria, and down-regulation of MAPK and Akt signal transduction, through the cGMP/PKG pathway. Therefore, this study implicates that BNP may have a therapeutic role in pulmonary vascular remodeling. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 10/2013; · 2.38 Impact Factor
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    ABSTRACT: OBJECTIVES: The present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in-exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD). METHODS: A prospective study was conducted in the pediatric intensive care unit. Children with NMD and ARF treated by combined NIV and MIE were included. Treatment success was defined as freedom from tracheal intubation during the hospital stay. Physiologic indices including PaO2 , PaCO2 , pH, and PaO2 /FiO2 were recorded before and 12, 24 hr after the use of NIV/MIE. RESULTS: Combined NIV/MIE was used in 15 NMD children (mean: 8.1 years, range: 3 months to 18 years) with 16 cases of ARF. There was no mortality in this cohort. Treatment success was achieved in 12 cases (75%), including six cases (38%) demanding "Do Not Intubate." ARF was due to pneumonia, with a mean baseline PaCO2 of 73.2 ± 19.0 mmHg. In the success group, hypercarbia and acidosis improved after use of NIV/MIE for 24 hr (PaCO2 : 71.7 ± 18.6 mmHg vs. 55.8 ± 11.6 mmHg, P < 0.01; pH: 7.29 ± 0.07 vs. 7.38 ± 0.05, P < 0.01). All patients tolerated NIV/MIE well despite transient skin pressure sores in five cases. CONCLUSIONS: Combined NIV/MIE is a safe and effective approach to rapidly improve physiologic indices and decrease the need for intubation in NMD children with ARF. NIV/MIE provides a good alternative for those refusing intubation. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 06/2013; · 2.38 Impact Factor
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    ABSTRACT: Botulism is a severe neuroparalytic illness which is difficult to diagnose accurately, especially in children. We report a child with type A botulism intoxication, with very rapid progression to coma-like consciousness and respiratory failure. Careful physical examinations led to the suspicion of botulism, and electrophysiologic examinations, including electroencephalogram and repetitive nerve stimulation tests, further supported the diagnosis. Hospitalization due to botulism had a great emotional impact on the patient and psychological support was crucial.
    Pediatrics & Neonatology 06/2013; · 0.93 Impact Factor
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    ABSTRACT: Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype–phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10–13 kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10–11 kb, with normal length being 50–300 kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention.
    Neuromuscular Disorders 01/2013; · 3.46 Impact Factor
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    ABSTRACT: KMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE) 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.7 cells and bone loss induced by ovariectomy in mice, and the underlying mechanisms. In vitro, KMUP-1 inhibited RANKL-induced TRAP activity, the formation of multinucleated osteoclasts and resorption-pit formation. It also inhibited key mediators of osteoclastogenesis including IL-1β, IL-6, TNF-α and HMGB1. In addition, KMUP-1 inhibited RANKL-induced activation of signaling molecules (Akt, MAPKs, calcium and NF-κB), mRNA expression of osteoclastogensis-associated genes (TRAP, MMP-9, Fra-1, and cathepsin K) and transcription factors (c-Fos and NFATc1). Furthermore, most inhibitory effects of KMUP-1 on RANKL-mediated signal activations were reversed by a protein kinase A inhibitor (H89) and a protein kinase G inhibitor (KT5823). In vivo, KMUP-1 prevented loss of bone mineral content, preserved serum alkaline phosphate and reduced serum osteocalcin in ovariectomized mice. KMUP-1 inhibits RANKL-induced osteoclastogenesis in vitro and protects against ovariectomy-induced bone loss in vivo. These effects are mediated, at least in part, by cAMP and cGMP pathways. Therefore, KMUP-1 may have a role in pharmacologic therapy of osteoporosis.
    PLoS ONE 01/2013; 8(7):e69468. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVE: Inflammation is an important molecular basis of atherosclerosis. Recent studies have shown that dihydropyridine calcium channel blockers (CCBs) can exert potent anti-inflammatory effects in models of vascular dysfunction. The purpose of the present study was to evaluate anti-inflammatory effects and mechanisms of lercanidipine and labedipinedilol-A, new generation dihydropyridine CCBs, in rat vascular smooth muscle cells (VSMCs) exposed to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). METHODS AND RESULTS: MTT, Griess reagent, RT-PCR, ELISA, gelatin zymography, immunocytochemistry and Western blotting were employed. We found that lercanidipine and labedipinedilol-A attenuated production of NO, ROS and TNF-α from LPS/IFN-γ-stimulated VSMCs. In addition, they both diminished the LPS/IFN-γ-induced expression of iNOS protein and mRNA, with attenuation of HMGB1 cytosolic translocation and subsequent extracellular release. Furthermore, they down-regulated MMP-2/MMP-9 activities, whereas expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9, was up-regulated. Finally, we found that lercanidipine and labedipinedilol-A inhibited the nuclear translocation of NF-κB and suppressed the phosphorylation of JNK, p38 MAPK and Akt. CONCLUSION: Lercanidipine and labedipinedilol-A can exert their anti-inflammatory effects through suppression of NO, ROS and TNF-α through down-regulation of iNOS, MMP-2/MMP-9, and HMGB1, with inhibition of signaling transduction of MAPKs, Akt/IkB-α and NF-κB pathways. These findings implicate a valuable role of new generation dihydropyridine CCBs lercanidipine and labedipinedilol-A for the treatment of inflammatory vascular diseases.
    Atherosclerosis 12/2012; · 3.71 Impact Factor
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    ABSTRACT: Hypertension can induce left ventricular hypertrophy (LVH), and the nitric oxide (NO) pathway plays an important role in the pathogenesis of cardiac hypertrophy. This study aimed to examine whether KMUP-1, a novel xanthine-based derivative, could inhibit LVH in spontaneously hypertensive rats (SHRs) and to investigate potential mechanisms underlying its antihypertrophic effects. Two groups of animals with chronic or subacute LVH were treated. In the chronic LVH group, KMUP-1 (10 or 30 mg/kg/d orally) was administered for 28 days to both normotensive rats and SHRs. In the subacute LVH group, KMUP-1 (0.5 mg/kg/d intraperitoneally) or sildenafil (0.7 mg/kg/d intraperitoneally) was administered for 10 days with or without co-treatment with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-l-arginine (L-NNA; 20 mg/L orally). After treatment, the effects of KMUP-1 or sildenafil on hypertension, cardiac hypertrophy, survival, expression of the NO/soluble guanylate cyclase (sGC)/protein kinase G (NO/sGC/PKG) pathway in the aorta andleft ventricle, and calcineurin A/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the left ventricle were examined. In the chronic LVH group, the SHRs developed hypertension with LVH over the 28 days. KMUP-1 attenuated the hypertension and LVH, increased survival rate, enhanced endothelial NOS/cyclic guanosine monophosphate/PKG (eNOS/cGMP/PKG) and decreased inducible NOS (iNOS) expression in the aorta and left ventricle of the SHRs. In the subacute LVH group, both KMUP-1 and sildenafil administered for 10 days attenuated the LVH in SHRs, with enhanced eNOS/cGMP/PKG and suppressed iNOS/calcineurin A/ERK1/2 expression in the left ventricle. In addition, both KMUP-1 and sildenafil attenuated L-NNA-induced LVH. KMUP-1 inhibition of hypertension-induced LVH with associated upregulation of eNOS, downregulation of iNOS in both the aorta and left ventricle, and attenuation of calcineurin A and ERK1/2 signaling in the left ventricle.
    The Kaohsiung journal of medical sciences 11/2012; 28(11):567-76. · 0.50 Impact Factor
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    ABSTRACT: Posterior reversible encephalopathy syndrome (PRES), first reported by Hinchey et al. in 1996, is an emerging neurological illness. It is characterized by headache, altered consciousness, visual disturbance, and seizures, with typical radiographic findings of vasogenic edema involving the posterior cerebral region. With widespread utilization of magnetic resonance imaging (MRI), PRES is becoming more familiar to adult phy-sicians. However, because of the relatively sparse number and relatively recent appearance of reports on PRES in the pediatric literature compared to the adult literature, this condition is less well addressed in field of pediatric critical care. Between 2005 and 2011, seven children (age 7–17 years) admitted to our pediatric intensive care unit (PICU) with a confirmed diagnosis of PRES were retrospectively investi-gated. Their initial and follow-up data, including underlying diseases, precipitating factors, clinical mani-festations, neuroimaging characteristics, and outcomes, were analyzed. The underlying diseases included collagen diseases, glomerulonephritis, renovascular hypertension, and malignancies. Hypertensive crisis occurred in five patients. The initial MRI scans of all patients showed typical vasogenic edema dis-tributed in the subcortical white matter of the parieto-temporo-occipi-tal regions. Moreover, six patients also had atypical MRI lesions, such as atypical distribution, cytotoxic edema, and abnormal contrast enhancement. After meticulous treatment with antihypertensive agents, anti-epileptics, and the with-holding of potential offending medications, all patients achieved complete clinical recovery with sub-sequent radiological resolution. To our knowledge, this is the first case series to describe PRES in the set-ting of PICU.
    Intensive Care Medicine 09/2012; · 5.54 Impact Factor
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    ABSTRACT: To evaluate the effects on neonatal outcomes between very-low-birth-weight (VLBW) preterm newborns with and without maternal use of antenatal corticosteroids (ACS). We retrospectively reviewed medical records of VLBW premature infants who were admitted to Kaohsiung Medical University Hospital between 1999 and 2008. A total of 256 infants were enrolled in this study. A total of 174 neonates did not receive any ACS, and 82 neonates received ACS. A total of 37 neonates received one dose of ACS, and 45 neonates received more than one dose of ACS, referred to as "multiple-dose ACS." In addition, these 82 infants were divided to betamethasone group (n=8) and dexamethasone group (n=50) with 24 infants excluded because of inadequate information. Neonates with multiple-dose ACS had lower incidence of surfactant use and lower rate of intubation than neonates without ACS. There were no differences in the occurrences of intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and chronic lung disease with one-dose vs. multiple-dose ACS and in the betamethasone group vs. the dexamethasone group. ACS reduces the need for exogenous surfactant, and the need for endotracheal tube insertion at birth in VLBW premature infants.
    Pediatrics & Neonatology 06/2012; 53(3):178-83. · 0.93 Impact Factor
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    ABSTRACT: Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R-induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways.
    Journal of Natural Medicines 04/2012; 66(2):311-20. · 1.52 Impact Factor
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    Cardiac Arrhythmias - New Considerations, 02/2012; , ISBN: 978-953-51-0126-0
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    ABSTRACT: Unilateral hyperlucent lung on chest radiograph is uncommon in children. It is often found incidentally and always refers to Swyer-James syndrome, with decrease in pulmonary vascularity and air trapping during expiration. However, it may occasionally mimic other serious lung diseases such as pulmonary hypoplasia/aplasia, defect of pulmonary artery, and other primary pulmonary disorders. In this study, we hypothesized that there would be characteristic patterns in pulmonary ventilation and perfusion scintigraphy (V/Q scan) in children with unilateral hyperlucency on chest film, which could play an important role in differential diagnosis of this disease group explicitly. Children with unilateral hyperlucency on chest radiograph had a detailed clinical examination and underwent echocardiography, chest computed tomography, selective pulmonary angiogram, flexible bronchoscopy, and pulmonary V/Q scan. A total of 10 cases were enrolled, including two cases of unilateral pulmonary artery agenesis, three cases of Swyer-James syndrome, two cases of agenesis of the right lung, one case of lobar emphysema, and two cases of tetralogy of fallot with left pulmonary artery stenosis. Besides, an overview of children with unilateral hyperlucent lung is provided, reviewing nine studies (171 patients), including our clinical experience, and finally an algorithm for diagnosis unilateral hyperlucent lung is proposed, based on the characteristics of V/Q scan. We chose a descriptive approach to the V/Q scan in children with unilateral hyperlucent lung on chest radiograph. This result enables us to promote the V/Q scan as a first-line tool in evaluating these patients and to avoid further unnecessary procedures.
    Nuclear Medicine Communications 08/2011; 32(11):1052-9. · 1.38 Impact Factor
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    ABSTRACT: Using various animal models, studies have greatly expanded our understanding of perinatal hypoxia-induced neuronal injury in the newborn at the cellular/molecular levels. However, the synapse-basis pathogenesis and therapeutic strategy for such detrimental alterations in the neonatal brain remain to be addressed. We investigated whether the damaged synaptic efficacy and neurogenesis within hippocampal CA1 region (an essential integration area for mammalian learning and memory) of the neonatal rat brain after perinatal hypoxia were restored by granulocyte-colony stimulating factor (G-CSF) therapy. Ten-day-old (P10) rat pups were subjected to experimentally perinatal hypoxia. G-CSF (10, 30, or 50 μg/kg, single injection/d, P11-16) was s.c. administered to neonatal rats which were analyzed on P17. Perinatal hypoxia reduced the expression in pRaf-pERK1/2-pCREB(Ser-133) signaling, the synaptic complex of postsynaptic density protein-95 (PSD-95) with N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), synaptic efficacy, and neurogenesis. A representatively effective dosage of G-CSF (30 μg/kg) alleviated the perinatal hypoxia-induced detrimental changes and improved the performance in long-term cognitive function. In summary, our results suggest a novel concept that synaptic efficacy defects exist in the neonatal brain previously exposed to perinatal hypoxia and that G-CSF could be a clinical potential for the synapse-basis recovery in the perinatal hypoxia suffers.
    Pediatric Research 08/2011; 70(6):589-95. · 2.67 Impact Factor
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    ABSTRACT: Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis. VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis. Labedipinedilol-A attenuated lysoPC-induced cell death and Ca(2+) influx. It also reduced reactive oxygen species (ROS) production evoked by lysoPC and down-regulated expressions of NAD(P)H oxidase subunits, Nox1 and Rac1. Moreover, it inhibited lysoPC-induced phosphorylation of MAPK including ERK1/2, JNK, and p38. It mitigated the dissipation of mitochondrial transmembrane potential induced by lysoPC. Lastly, labedipinedilol-A inhibited lysoPC-induced apoptosis with attenuation of caspase-3/-9 activations and modulation of Bax/Bcl-2 protein expressions. Labedipinedilol-A can suppress lysoPC-induced VSMCs death via reducing ROS production and anti-apoptosis. These protective effects are potentially mediated through the inhibition of Ca(2+) influx, down-regulation of the NAD(P)H oxidase subunits (Nox1/Rac1) and MAPK signaling, and attenuation of mitochondrial depolarization. Thus, labedipinedilol-A may have a valuable role in the preventing atherosclerosis associated with hyperlipidemia.
    Atherosclerosis 05/2011; 217(2):379-86. · 3.71 Impact Factor
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    ABSTRACT: San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg(-1): 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg(-1): 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.
    Evidence-based Complementary and Alternative Medicine 01/2011; 2011:915051. · 1.72 Impact Factor

Publication Stats

118 Citations
140.44 Total Impact Points

Institutions

  • 2002–2014
    • Kaohsiung Medical University
      • • Department of Pediatrics
      • • College of Medicine
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2011–2013
    • Chia Nan University of Pharmacy and Science
      • Department of Pharmacy
      Tainan, Taiwan, Taiwan
  • 2007
    • McGill University
      Montréal, Quebec, Canada
  • 2005
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2004
    • Kuo General Hospital
      臺南市, Taiwan, Taiwan