Association between transforming growth factor-beta and hypertension

Discordant findings are reported on the left ventricular transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in various rat models. Left ventricular TGF-beta(1) mRNA levels did not differ between spontaneously hypertensive rats (SHR) and normal rats, between deoxycorticosterone (DOCA)-salt and sham-operated hypertensive rats, but were increased in stroke-prone spontaneously hypertensive rats (SHRSP) and in post-myocardial infarction (MI) rats. Renal cortical TGF-beta(1) mRNA levels were, however, higher in DOCA-salt hypertensive rats. Angiotensin II subtype 1 receptor antagonism (AT(1)R) and angiotensin converting enzyme inhibition (ACEI) decreased left ventricular and vascular smooth muscle TGF-beta(1) mRNA levels in SHR and renal TGF-beta(1) mRNA in DOCA-salt hypertensive rats and in SHRSP. In post-MI rats ventricular TGF-beta(1) mRNA decreased by AT(1)R antagonism. In essential hypertensive patients, TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are hyperexpressed. The TGF-beta(1) overproduction in hypertension can be attributed to various factors such as elevated angiotensin II, increased systemic blood pressure (BP) per se, increased fluid shear stress and a differential expression of TGF-beta(1) linked to DNA polymorphism in the promoter. The Arg(25) polymorphism in the TGF-beta(1) gene is associated with higher BP. A higher plasma TGF-beta(1) concentration is found in hypertensive patients with microalbuminuria and left ventricle hypertrophy. In these patients, AT(1)R antagonism and ACEI reduced these plasma TGF-beta(1) levels significantly.     

Downstream factors in transforming growth factor-beta family signaling

The recently identified family of Smad proteins has given insight in the understanding of how members of the transforming growth factor-beta (TGF-beta) family relay their signal to the nucleus. Besides Smad proteins, G proteins and MAPKs are also involved in the downstream signaling of TGF-beta family members. The identification of elements that function downstream in the TGF-beta signaling pathway and the fact that these downstream players can interact with the signaling cascade of other growth factors, may give insight into the diverse biological responses evoked by the TGF-beta family members.     

Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension

OBJECTIVE: We explored the potential role of the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) in patients with idiopathic pulmonary arterial hypertension (IPAH). Method and Results- We correlated plasma ADMA levels and cardiovascular indices from right heart catheterization in 57 patients with IPAH. Predictors of survival in patients with IPAH were studied. Furthermore, the effect of systemic ADMA infusion on pulmonary ventricular resistance and stroke volume was investigated in healthy volunteers using right heart catheterization. Mean plasma ADMA concentrations were significantly higher in patients with IPAH than in control subjects (0.53+/-0.15 versus 0.36+/-0.05 micromol/L; P<0.001). ADMA plasma concentrations correlated significantly with indices of right ventricular function, such as mixed-venous oxygen saturation (r=-0.49; P<0.0001), right atrial pressure (r=0.39; P<0.003), cardiac index (r=-0.35; P<0.008), as well as survival (r=-0.47; P<0.0001). Multiple regression analysis revealed that right atrial pressure (r=0.31; P<0.026) and ADMA (r=0.29; P<0.039) were independent predictors of mortality. Moreover, patients with supra-median plasma ADMA levels had significantly (P<0.021) worse survival than patients with infra-median ADMA values. ADMA infusion in healthy volunteers increased pulmonary vascular resistance (68.9+/-7.6 versus 95.6+/-6.3 dyne x s x cm(-5); P<0.05) and decreased stroke volume (101.1+/-6.7 mL versus 95.6+/-6.3 mL; P<0.05). CONCLUSIONS: Increased ADMA plasma levels are associated with unfavorable pulmonary hemodynamics and worse outcome in patients with IPAH.     

Increased levels of transforming growth factor-beta1 in essential hypertension

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that has been linked to vascular remodeling processes, myocardial hypertrophy, and renal fibrosis. Recently a correlation between serum levels of TGF-beta1 and blood pressure (BP) levels in patients with end-stage renal disease was shown. In addition, it is not clear whether TGF-beta1 is a causative factor in the pathogenesis of essential hypertension and associated with hypertensive target organ damage (TOD). METHODS: Using a TGF-beta1-specific sandwich ELISA, we compared plasma levels of active and total TGF-beta1 of 30 normotensive persons and 85 patients with essential hypertension with and without TOD, as measured by microalbuminuria or left ventricular hypertrophy. RESULTS: Active and total TGF-beta1 levels were significantly higher in plasma of patients with essential hypertension than in normotensive controls (P < .05 and P < .01, respectively). However, neither active nor total TGF-beta1 correlated with systolic or diastolic BP (R2 < 0.14 for all parameters). Levels of active and total TGF-beta1 were significantly higher in hypertensive patients with than without TOD (P < .05). CONCLUSIONS: Active and latent TGF-beta1 levels are markedly increased in plasma of hypertensive patients. We assume that TGF-beta1 contributes substantially to the development of TOD in essential hypertension, independent of BP levels.     

特发性肺动脉高压一例临床分析

特发性肺动脉高压（idiopathic pulmonary arterial hypertension,IPAH）是一种罕见的、进行性加重、原因不明的肺动脉血管硬化病变,诊断往往比较困难,预后险恶。至今全世界约有1000多例报道,我国尚无精确统计,但也有散在报道。2010年我院收治1名患者,现将其临床资料进行回顾性分析。     

Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to determine if pulmonary vascular capacitance predicts survival in patients with idiopathic pulmonary arterial hypertension (IPAH). BACKGROUND: The prognosis of patients with IPAH is difficult to predict, despite knowledge of clinical and hemodynamic parameters previously identified as predictors. METHODS: We proposed a capacitance index of stroke volume divided by pulmonary pulse pressure (SV/PP) and prospectively gathered data on IPAH patients who underwent a right heart catheterization. SV/PP was analyzed as a predictor of mortality after adjusting for other modifiers of risk. RESULTS: During 4-year follow-up of 104 patients, 21 patients died. When compared with conventional markers, SV/PP was the strongest univariate predictor of mortality (hazard ratio 17.0 per ml.mm Hg(-1) decrease, 95% confidence interval 13.0 to 22.0; p < 0.0001). In successive bivariate analysis, SV/PP was the only predictor of mortality. In quartile analysis, the lowest SV/PP quartile had a 4-year mortality of 61%; the highest SV/PP had no deaths. CONCLUSIONS: The capacitance index (SV/PP) is a strong independent predictor of mortality in patients with IPAH.     

New predictors of outcome in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.