刘晓妍
北京大学第一医院 心血管内科
Background:Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition that affects multiple organs and systems.Case summary:A 51-year-old man with a history of occult left apex myocardial infarction diagnosed based on electrocardiographic and echocardiographic findings underwent coronary computed tomography (CT) angiography for the evaluation of coronary artery disease; the findings revealed a soft-tissue mass that surrounded the aortic root and the distal portion of the left coronary artery. The mass was considered an inflammatory lesion; high glucose uptake on positron emission tomography/CT supported this assumption. Coronary angiography revealed 80% stenosis of the distal portion of the left anterior descending artery, which corresponded with the infarction. Intravascular ultrasound revealed hypoechoic regions outside the lumina of the stenotic segment. Based on these findings, IgG4-related periaortitis/periarteritis was suspected; the patient was accordingly treated with oral prednisone and methotrexate. At the 3-month follow-up, the periaortic mass had slightly reduced in size.Discussion:Identification and diagnosis of IgG4-related cardiovascular disease are challenging; cases with localized coronary artery involvement may be misdiagnosed as atherosclerotic coronary artery disease. Although imaging techniques, including intracoronary imaging, may aid in differential diagnosis, their sensitivity and specificity still warrant further studies. Practical criteria that facilitate diagnosis and a better understanding of the disease are required.
European heart journal. Case reports 2022
Recent studies reported some long noncoding RNAs (lncRNAs)-mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs. AK098656 promoted VSMCs synthetic phenotype evidenced by increasing VSMC proliferation and migration, elevating extracellular matrix proteins, whereas lowering contractile proteins. Furthermore, AK098656 was demonstrated to directly bind with the VSMCs-specific contractile protein, myosin heavy chain-11, and an essential component of extracellular matrix, fibronectin-1, and finally lowered these protein levels through protein degradation. AK098656 was also shown to bind with 26S proteasome non-ATPase regulatory subunit 11 and facilitated myosin heavy chain-11 to interact with this protein. In vivo, AK098656 transgenic rats showed spontaneous development of hypertension, with elevated VSMCs synthetic phenotype and narrowed resistant arteries. Transgenic rats also showed slight cardiac hypertrophy without other complications, which was similar with early pathophysiological changes of hypertension. All these data indicated AK098656 as a new human VSMC-dominant lncRNA, which could promote hypertension through accelerating contractile protein degradation, increasing VSMC synthetic phenotype, and finally narrowed resistance arteries.
Hypertension (Dallas, Tex. : 1979) 2018
BACKGROUND:Recent studies suggest that variants in two calcium handling genes (RyR2 and CASQ2) associated with sudden cardiac death (SCD) and non-sudden cardiac death (NSCD) in subjects with heart failure and coronary artery disease, respectively. The purpose of this study was to identify other calcium handling genes associated with SCD in the long-term of chronic heart failure (CHF) in Chinese Han population.METHODS AND RESULTS:We investigated 20 SNPs representing 10 genes that regulated calcium handling in 1429 patients with CHF, and the genetic association with SCD and all-cause death was analysed. During a median follow-up period of 63 months, 538 patients (37.65%) died from CHF, of whom 185 (34.38%) had SCD and the others were NSCD. SNPs that pass a P value cut-off of 0.0025 were considered as significant. We found that patients carrying the CC genotype of rs3814843 on CALM1 gene had greater risks of SCD (HR 5.542, 95% CI 2.054-14.948, P = .001) and all cause death (HR 3.484, 95% CI 1.651-7.350, P = .001). After adjusting for other risk factors, significant associations remained. Moreover, patients carrying G allele of rs361508 on TRDN gene also had increased risk of SCD.CONCLUSIONS:Common variants in TRDN and CALM1 are associated with increased risk of SCD in patients with CHF. These findings provide further evidence for association of variants in calcium handling regulating proteins and SCD in chronic heart failure.
PloS one 2015
Aminoglycosides promote the readthrough of premature stop codons introduced by nonsense mutations to produce full-length proteins in genetic disease models. The read-through effects of different aminoglycosides and PTC124 on HERG gene have yet to be adequately elucidated. The wild-type (WT) or mutant genes were transiently transfected in HEK293 cells. The read-through effect was examined by adding drugs into culture medium for 24 h. Western blot analysis and patch clamping were performed to evaluate the expression and function of the genes. The mRNA levels were determined using qPCR. The results showed that G418 and PTC124 significantly increased the protein expression of R1014X mutant in a dose-dependent manner and produced a full-length protein. The maximal protein levels after G418, gentamicin or PTC124 treatment were 39.1±2.4, 18.6±0.3 or 10.3±1.0%, respectively, of the WT level. Tobramycin did not exhibit a read-through effect. The mRNA levels, however, did not differ between WT and mutant gene. The tail current densities of R1014X channels at 40 mV were 22.57±2.26 pA/pF for G418, 16.21±1.49 pA/pF for gentamicin and 9.62±0.73 pA/pF for PTC124. The leftward shift of the activation curve was corrected only by G418 and gentamicin. The read-through effects of W927X, R863X and E698X revealed that as the mutation site approached the N-terminal, the rescue efficiency was decreased. The above results suggest that aminoglycosides and PTC124 induced different effects on rescue nonsense mutations of the HERG gene. The mutation site was a significant factor in determining the pharmacological rescue efficiency.
International journal of molecular medicine 2014
AIMS:Chronic heart failure with reduced ejection fraction (CHF-REF) remains a major public health problem with high morbidity and mortality, but the data on current treatment status and long-term prognosis in China were still missing.METHODS:Among prospectively recruited 2368 patients with CHF-REF in 10 hospitals, 2154 patients provided complete followed data. Two aetiology subgroups (dilated cardiomyopathy, DCM and ischaemic cardiomyopathy, ICM) were classified. Clinical data and long-term prognosis were analysed.RESULTS:After a median follow-up of 52 months, 850 (39.46%) patients died, of whom 302 (35.53%) were sudden cardiac death (SCD). Unadjusted rates of all-cause mortality and SCD were higher in DCM than those in ICM (p<0.001 for both modes of death), but mortalities were comparable after adjustment for co-variables (p=0.387 and p=0.483 respectively). ACEIs/ARBs, aldosterone receptor antagonists, β-blockers and diuretics were dominant prescribed drugs with the prescription rates of 65.97%, 74.61%, 68.29% and 74.37% respectively. Multivariable analysis identified co-morbidities (eg, hypertension), NHYA class, ventricular tachycardia/fibrillation (VT/VF), QRS duration, left ventricular EF and creatinine as independent predictors of mortalities, whereas ACEIs/ARB, β-blockers and statins were associated with better prognosis. Survived from sustained VT/VF episodes had the highest predictive value for SCD (HR, 4.230; 95% CI, 2.500-7.157; p<0.001). The predictors for mortalities in DCM and ICM were different.CONCLUSIONS:Patients with CHF-REF had a poor prognosis in China despite being under current standard therapies, especially patients with DCM. Predictors for all-cause mortality and SCD might be identified for evaluating the prognosis of these patients.
Heart, lung & circulation 2014
OBJECTIVES:The variation of the substrates of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) was not understood. The purpose of this study was to investigate the variation of electroanatomic substrate [slow conduction zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control individuals and markers of successful ablation.METHODS:Electroanatomical mapping was performed during sinus rhythm in 20 ILVT patients and 26 control individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were tagged in geometry and the anatomic aspects were investigated.RESULTS:According to the distribution of Purkinje potential, LVCS was distinguished into three types: left bundle branch (LBB) was divided into two discrete fascicles without interconnections; divided into three separate fascicles; and fanlike structure distribution over septum broadly. The length of LBB and its fascicles in patients with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT group, the SCZ was located at the inferoposterior septum in 17, inferior apical septum in one and two SCZs were located at the posterior and mid-septal in the other two patients, which were greater in size and longer in length than those of six controls (P < 0.05). At the crossover junction area with diastolic potential and Purkinje potential, with the size of 1.5 ± 0.4 cm(2), concealed entertainment and ablation were obtained successfully in all patients with ILVT.CONCLUSION:The anatomy of the LVCS and SCZ is highly variable in patients with ILVT, and the crossover junction area with diastolic potential and Purkinje potential might be a marker of ablation.
Journal of cardiovascular medicine (Hagerstown, Md.) 2014
The purpose of this study was to evaluate whether CC-AAbs levels could predict prognosis in CHF patients. A total of 2096 patients with CHF (841 DCM patients and 1255 ICM patients) and 834 control subjects were recruited. CC-AAbs were detected and the relationship between CC-AAbs and patient prognosis was analyzed. During a median follow-up time of 52 months, there were 578 deaths. Of these, sudden cardiac death (SCD) occurred in 102 cases of DCM and 121 cases of ICM. The presence of CC-AAbs in patients was significantly higher than that of controls (both P < 0.001). Multivariate analysis revealed that positive CC-AAbs could predict SCD (HR 3.191, 95% CI 1.598-6.369 for DCM; HR 2.805, 95% CI 1.488-5.288 for ICM) and all-cause mortality (HR 1.733, 95% CI 1.042-2.883 for DCM; HR 2.219, 95% CI 1.461-3.371 for ICM) in CHF patients. A significant association between CC-AAbs and non-SCD (NSCD) was found in ICM patients (HR = 1.887, 95% CI 1.081-3.293). Our results demonstrated that the presence of CC-AAbs was higher in CHF patients versus controls and corresponds to a higher incidence of all-cause death and SCD. Positive CC-AAbs may serve as an independent predictor for SCD and all-cause death in these patients.
Disease markers 2014
BACKGROUND:Variants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated.METHODS AND RESULTS:A total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rs12567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124-1.698 [P = .002], and HR 1.645, 95% CI 1.184-2.287 [P = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054-1.624 [P = .015], and HR 1.601, 95% CI 1.129-2.271 [P = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population (P = .026).CONCLUSIONS:The A allele of rs12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population.
Journal of cardiac failure 2014
Dermatopontin (DPT), an extracellular matrix (ECM) protein, has been previously shown to be upregulated in the infarct zone of experimentally induced myocardial infarction (MI) rats. However, the accurate role that DPT exerts in the ventricular remodeling process after MI remains poorly understood. In this study, we evaluated the expression pattern of DPT mRNA and protein as well as its secretion in cultured neonatal rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs) under conditions of hypoxia and serum deprivation (hypoxia/SD). Further, we tested the possible roles of DPT in CFs adhesion, spreading, migration and proliferation, which greatly promote the ventricular remodeling process after MI. Results showed that hypoxia/SD stimulated DPT expression and secretion in CMs and CFs and that DPT promoted adhesion, spreading and migration of CFs whereas had no effect on CFs proliferation. In addition, functional blocking antibodies specific for integrin α3 and β1 significantly reduced CFs adhesion and migration that DPT induced, suggesting that integrin α3β1 is at least one receptor for CFs adhesion and migration to DPT. These results implicated that DPT participates in the ventricular remodeling process after MI and may act as a potential therapeutic target for ventricular remodeling.
Matrix biology : journal of the International Society for Matrix Biology 2013
