1.The Effect of Hypertriglyceridemia on Vascular Endothelial Function
Yun HUANG ; Guizhu DAI ; Zongchen FENG ; Chengfa LU ; Bei CHENG ; Qiufen WANG ; Fuding NIE ; Jingdong LI
Chinese Journal of Hypertension 2004;12(2):120-122
Objective To investigate the effect of hypert riglyceridemia on vascular endothelial function. Methods With high-resolution ultrasound, flow and nitroglycerin-induced dilatation of the brachial artery were determined in thirty hypertriglyceridemic patients and thirty healthy subjects as controls. Serum lipid and plasma endothelin (ET) were determined. Results In patients with hypertriglyceridemia,flow-induced vasodilatation was much reduced compared with that in the control subjects[(2.7±2.0)% vs (15.0±8.0)%, P<0.001].However, vasodilatation in response to nitroglycerin were similar in both groups[(15.0±5.0)% vs (16.8±9.0)%, P>0.05].Plasma ET level in the hypertriglyceridemic group was significantly higher than that in the control group[(106.22±19.16) μg/L vs (72.37±14.06) μg/L, P<0.001].ConclusionEndothelium-dependent vasodilatation was impaired in patients with hypertriglyceridemia.
2.A case of Cryoballoon ablation for persistent atrial fibrillation.
Jian SUN ; Xiangfei FENG ; Pengpai ZHANG ; Jun WANG ; Rui ZHANG ; Zhiquan WANG ; Qiufen LU ; Bo LIU ; Shangbiao LU ; David LAN ; Yigang LI
Chinese Journal of Cardiology 2014;42(4):341-342
Aged
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Atrial Fibrillation
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surgery
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Catheter Ablation
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methods
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Humans
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Male
3.Identification of a new lamin A/C mutation in a chinese family affected with atrioventricular block as the prominent phenotype.
Xiaoyan, WU ; Qing K, WANG ; Le, GUI ; Mugen, LIU ; Xianqin, ZHANG ; Runming, JIN ; Wei, LI ; Lu, YAN ; Rong, DU ; Qiufen, WANG ; Jianfang, ZHU ; Junguo, YANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(1):103-7
Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of [Symbol: see text]50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.
4.Effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia.
Yun HUANG ; Guizhu DAI ; Zongchen FENG ; Chengfa LU ; Bei CHENG ; Qiufen WANG ; Fuding NIE ; Jingdong LI
Chinese Medical Journal 2003;116(11):1767-1769
OBJECTIVETo investigate the effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia.
METHODSUsing high-resolution ultrasound, we measured flow- and nitroglycerin-induced dilatation of the brachial artery in 30 patients with hypertriglyceridemia before and after treatment with micronized fenofibrate at a dose of 200 mg once daily for 4 weeks. Simultaneously, both serum lipid and plasma endothelin (ET) levels were determined.
RESULTSAfter micronized fenofibrate therapy, serum triglyceride (TG) levels decreased significantly (P < 0.05). Plasma ET levels also decreased markedly [(82.66 +/- 15.46) microg/L vs. (106.22 +/- 19.16) microg/L, P < 0.001]. Flow-induced vasodilatation was much improved (11.0% +/- 9.0% vs 2.7% +/- 2.0%, P < 0.01). However, no significant changes in vasodilatation occurred in response to nitroglycerin (16.2% +/- 6.0% vs 15.0% +/- 5.0%, P > 0.05) in patients with hypertriglyceridemia.
CONCLUSIONSMicronized fenofibrate can improve impaired endothelium-dependent vasodilatation in patients with hypertriglyceridemia. Improving endothelial function may also be the mechanism responsible for the beneficial effects of micronized fenofibrate.
Adult ; Endothelium, Vascular ; drug effects ; physiology ; Female ; Fenofibrate ; pharmacology ; therapeutic use ; Humans ; Hypertriglyceridemia ; drug therapy ; Male ; Middle Aged ; Vasodilation ; drug effects
5.Identification of a New Lamin A/C Mutation in a Chinese Family Affected with Atrioventricular Block as the Prominent Phenotype
WU XIAOYAN ; K.WANG QING ; GUI LE ; LIU MUGEN ; ZHANG XIANQIN ; JIN RUNMING ; LI WEI ; YAN LU ; DU RONG ; WANG QIUFEN ; ZHU JIANFANG ; YANG JUNGUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(1):103-107
Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA,which resulted in an E82K mutation.The E82K mutation co-segregated with all affected individuals in the family,and was not present in 200 normal controls.Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades.Ejection fractions were documented in 5 patients with DCM,but 4 showed a normal value of ≥50%.Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients.This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM.The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.
6.Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells.
Qiufen ZHANG ; Yingyi CHEN ; Duan NI ; Zhimin HUANG ; Jiacheng WEI ; Li FENG ; Jun-Cheng SU ; Yingqing WEI ; Shaobo NING ; Xiuyan YANG ; Mingzhu ZHAO ; Yuran QIU ; Kun SONG ; Zhengtian YU ; Jianrong XU ; Xinyi LI ; Houwen LIN ; Shaoyong LU ; Jian ZHANG
Acta Pharmaceutica Sinica B 2022;12(2):876-889
SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.