[Show abstract][Hide abstract] ABSTRACT: Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group.
We designed a cross-sectional study in 173 prevalent PD patients. LV diastolic dysfunction was diagnosed by echocardiography. PD patient without LV diastolic dysfunction served as the control group. Serum inflammatory biomarkers were examined including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The location and amount of adipose tissue were assessed by computerized tomography (CT) at the level of the fourth lumbar vertebra.
Subjects with LV diastolic dysfunction had higher levels of the pro-inflammation cytokines and more visceral and peritoneal fat (all P<0.001) than control subjects. A significant correlation was found between visceral adipose tissue and pro-inflammatory cytokines (r = 0.70; P<0.001). Multivariable regression analysis found that the relationship between visceral adipose tissue and LV diastolic dysfunction became insignificant when either TNF-α or IL-6 were introduced into the model, although TNF-α and IL-6 were both significantly associated with LV diastolic dysfunction even after adjusting for visceral fat (OR = 1.51; 95% CI = 1.09-2.02; P = 0.033 and OR = 1.62; 95% CI = 1.09-1.82; P = 0.031, respectively).
Larger amounts of adipose tissue were associated with higher serum pro-inflammatory levels in PD patients, which might be related to the development of LV diastolic dysfunction. Modulating inflammatory reactions in PD patients can be a useful therapeutic approach for managing LV diastolic dysfunction.
PLoS ONE 01/2013; 8(5):e62722. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for the mortality of critically ill patients. We investigated the possible molecular mechanism from inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) causing left ventricular (LV) diastolic dysfunction in critically burned patients. We consecutively enrolled 56 critically burned patients who were admitted to the intensive care unit and performed transthoracic echocardiography to evaluate LV diastolic function. Sarcoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) gene expression in HL-1 cardiomyocytes was used as a molecular phenotype of diastolic heart failure. Soluble plasma levels of TNF-α and IL-6 were measured in all subjects. The effect of serum from the burned patients on SERCA2 gene expression of HL-1 cardiomyocytes was investigated. The total body surface area of burned patients was proportional to serum level of IL-6 and TNF-α (P < 0.001 for each). Significant correlations were found for TNF-α and decelerating time, E/A, and E/Em (r² = 0.59, 0.45, and 0.52; P <0.001 for each) and for IL-6 and decelerating time, E/A, and E/Em (r² = 0.63, 0.60, and 0.62; P < 0.001 for each). Diastolic function improved significantly in association with decrease in cytokines after burned patients were transferred to general ward (P < 0.001). Tumor necrosis factor α, IL-6, and sera from critically burned patients downregulated the expression of the SERCA2 gene in HL-1 cardiomyocytes. There was a significant correlation between LV diastolic dysfunction and in-hospital mortality in critically burned patients (hazard ratio, 3.92; P = 0.034) after risk factors were adjusted. Inflammatory cytokines may be associated with cardiac diastolic, which could be an independent prognostic factor in burn patients. Novel therapeutic strategies may be applied in critically burned patients with LV diastolic dysfunction by modulating inflammatory reactions.
[Show abstract][Hide abstract] ABSTRACT: Myosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study.
A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≥ 5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene.
In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25-3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17-3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53-2.89); permuted p = 0.029).
We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population.
PLoS ONE 04/2012; 7(4):e35242. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The sarcoplasmic reticulum Ca(2+) ATPase (SERCA) is essential for the regulation of the intracellular calcium level in cardiomyocytes. Previous studies have found that angiotensin II (Ang II) decreased SERCA2 gene expression in ventricular myocytes. Alteration of SERCA activity is important in the mechanism of atrial fibrillation. The present study was undertaken to examine Ang II effects on atrial myocytes.
An approximately 1.75-kb promoter region of SERCA2 gene was cloned with the pGL3 luciferase vector. The direct effects of Ang II on SERCA2 gene expression in HL-1 atrial myocytes were examined by promoter activity assay, followed by Western blot analysis for protein levels and quantitative real-time reverse transcription polymerase chain reaction for mRNA amounts.
Ang II did not increase the promoter activity of the 1,754-bp promoter-receptor construct of the SERCA2 gene. The levels of SERCA2 protein and mRNA were also unchanged at different time points after Ang II treatment.
Although Ang II had prominent effects on SERCA2 in ventricular myocytes, it did not alter SERCA2 gene expression and protein levels in atrial myocytes. We provide a model for further investigation of the regulation of SERCA2 gene expression in atrial myocytes.
Journal of Renin-Angiotensin-Aldosterone System 08/2009; 10(3):121-6. · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microalbuminuria may be an early sign of intra-renal vascular dysfunction and a marker of vascular risk in the general population as well as in high-risk individuals. However, the association between albuminuria and PAD has been demonstrated only in few small studies. The aim of current study is to evaluate the relative impact of albuminuria and glomerular filtration rate on the risk of peripheral artery disease (PAD) in a nationally representative sample population. Data (ankle brachial index [ABI], urine albumin, fasting glucose, and glomerular filtration rate [GFR] estimated using the Modification of Diet in Renal Disease [MDRD] Study equation) were collected on 7068 adults from the National Health and Nutrition Examination Survey (NHANES 1999-2004). PAD was defined as ABI <0.9 or >1.4. There was a trend towards an association between the presence of abnormal renal function (GFR<60mL/min/1.73m(2)) and PAD in the non-diabetic patients (OR of 1.43, 95% CI: 0.98-2.09; P=0.07) where as the presence of abnormal renal function was strongly associated PAD in the diabetic patients (OR of 2.3, 95% CI: 1.34-3.95; P=0.046). On the contrary, albuminuria was independently associated with PAD in the non-diabetic (OR, 1.87; 95% CI, 1.38-2.52; P=0.0003) but not in the diabetic patients (OR: 1.08, 95% CI: 0.68-1.73, P=0.7411). We concluded that albuminuria, independent of renal function, is strongly associated with PAD in non-diabetic subjects. As diabetes develops and HbA1c level increases, the predictive value of albuminuria gradually diminishes after adjustment for renal function.
[Show abstract][Hide abstract] ABSTRACT: Whereas uterine leiomyoma is a common woman disease, intravenous leiomyomatosis with intracaval and intracardiac complications is a rare condition. The initial presentation is dependent upon the severity of the intracardiac involvement, although complete surgery is the best treatment. The case of a 39-year-old woman is described here, with an initial presentation of dyspnea and right heart failure. Leiomyomatosis originating from the uterus and extending to the inferior vena cava and right atrium was diagnosed from various preoperative studies. The patient was resuscitated because of respiratory failure and severe right heart failure. However, she was operated successfully through a two-stage approach and remained well postoperatively. This case illustrates an intriguing presentation of intravenous leiomyomatosis and a curative surgical intervention even in critical condition.
Internal Medicine 02/2009; 48(12):997-1001. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dysfunction of the autonomic nervous system is often encountered in the out-patient clinics of Family Medicine Departments. However, acute pandysautonomia including severe orthostatic hypotension, impaired gastrointestinal and bladder motility could be an uncommon variant of Guillian-Barré syndrome. A 49-year-old male with acute onset of pandysautonomia is reported. Neurophysiological testing and cerebral spinal fluid examination were performed and the GBS variant form was diagnosed. The patient s symptoms were relieved after the administration of intravenous immunoglobulins (IVIGs). These findings are consistent with a dysimmune pathogenesis for the syndrome and suggest a possible treatment and diagnosis process for future cases. (Taiwan J Fam Med 2008; 18: 248-53)
Taiwan Journal of Family Medicine. 10/2008; 18(4):248-253.