Description: Background We aimed to explore the role of endogenous sulfur dioxide (SO 2 ) in pulmonary vascular collagen remodeling induced by monocrotaline and its mechanisms. Methods and Results A rat model of monocrotaline-induced pulmonary vascular collagen remodeling was developed and administered with l -aspartate-β-hydroxamate or SO 2 donor. The morphology of small pulmonary arteries and collagen metabolism were examined. Cultured pulmonary arterial fibroblasts stimulated by transforming growth factor β1 (TGF-β1) were used to explore the mechanism. The results showed that in monocrotaline-treated rats, mean pulmonary artery pressure increased markedly, small pulmonary arterial remodeling developed, and collagen deposition in lung tissue and pulmonary arteries increased significantly in association with elevated SO 2 content, aspartate aminotransferase (AAT) activity, and expression of AAT1 compared with control rats. Interestingly, l -aspartate-β-hydroxamate, an inhibitor of SO 2 generation, further aggravated pulmonary vascular collagen remodeling in monocrotaline-treated rats, and inhibition of SO 2 in pulmonary artery smooth muscle cells activated collagen accumulation in pulmonary arterial fibroblasts. SO 2 donor, however, alleviated pulmonary vascular collagen remodeling with inhibited collagen synthesis, augmented collagen degradation, and decreased TGF-β1 expression of pulmonary arteries. Mechanistically, overexpression of AAT1, a key enzyme of SO 2 production, prevented the activation of the TGF-β/type I TGF-β receptor/Smad2/3 signaling pathway and abnormal collagen synthesis in pulmonary arterial fibroblasts. In contrast, knockdown of AAT1 exacerbated Smad2/3 phosphorylation and deposition of collagen types I and III in TGF-β1–treated pulmonary arterial fibroblasts. Conclusions Endogenous SO 2 plays a protective role in pulmonary artery collagen accumulation induced by monocrotaline via inhibition of the TGF-β/type I TGF-β receptor/Smad2/3 pathway.

Description: Background Recent longitudinal work suggests that weight change is an important risk factor for inflammation across the full range of BMI. However, few studies have examined whether the risk of inflammation differs by patterns of weight gain over time. Using latent class trajectory analysis, we test whether patterns of weight gain are associated with elevated high-sensitivity C-reactive protein (hs-CRP 2–10 mg/L). Methods and Results Data come from China Health and Nutrition Survey (CHNS) participants (n=5536), aged 18 at baseline to 66 years in 2009, with measured weight over 18 years. Latent class trajectory analysis was used to identify weight-change trajectories in 6 age and sex strata. Multivariable general linear mixed-effects models fit with a logit link were used to assess the risk of elevated hs-CRP across weight trajectory classes. Models were fit within age and sex strata, controlling for baseline weight, adult height, and smoking, and included random intercepts to account for community-level correlation. Steeper weight-gain trajectories were associated with greater risk of elevated hs-CRP compared to more moderate weight-gain trajectories in men and women. Initially high weight gain followed by weight loss was associated with lower risk of elevated hs-CRP in women aged 18 to 40. Conclusions Latent class trajectory analysis identified heterogeneity in adult weight change associated with differential risk of inflammation independently of baseline weight and smoking. These results suggest that trajectories of weight gain are an important clinical concern and may identify those at risk for inflammation and the development of cardiometabolic disease.

Description: BackgroundWe aimed to explore the role of endogenous sulfur dioxide (SO2) in pulmonary vascular collagen remodeling induced by monocrotaline and its mechanisms.Methods and ResultsA rat model of monocrotaline‐induced pulmonary vascular collagen remodeling was developed and administered with l‐aspartate‐β‐hydroxamate or SO2 donor. The morphology of small pulmonary arteries and collagen metabolism were examined. Cultured pulmonary arterial fibroblasts stimulated by transforming growth factor β1 (TGF‐β1) were used to explore the mechanism. The results showed that in monocrotaline‐treated rats, mean pulmonary artery pressure increased markedly, small pulmonary arterial remodeling developed, and collagen deposition in lung tissue and pulmonary arteries increased significantly in association with elevated SO2 content, aspartate aminotransferase (AAT) activity, and expression of AAT1 compared with control rats. Interestingly, l‐aspartate‐β‐hydroxamate, an inhibitor of SO2 generation, further aggravated pulmonary vascular collagen remodeling in monocrotaline‐treated rats, and inhibition of SO2 in pulmonary artery smooth muscle cells activated collagen accumulation in pulmonary arterial fibroblasts. SO2 donor, however, alleviated pulmonary vascular collagen remodeling with inhibited collagen synthesis, augmented collagen degradation, and decreased TGF‐β1 expression of pulmonary arteries. Mechanistically, overexpression of AAT1, a key enzyme of SO2 production, prevented the activation of the TGF‐β/type I TGF‐β receptor/Smad2/3 signaling pathway and abnormal collagen synthesis in pulmonary arterial fibroblasts. In contrast, knockdown of AAT1 exacerbated Smad2/3 phosphorylation and deposition of collagen types I and III in TGF‐β1–treated pulmonary arterial fibroblasts.ConclusionsEndogenous SO2 plays a protective role in pulmonary artery collagen accumulation induced by monocrotaline via inhibition of the TGF‐β/type I TGF‐β receptor/Smad2/3 pathway.