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Objective:To explore the effects of different concentrations of 2-hydroxybenzylamine(2-HOBA)on atherosclerosis and vascular smooth muscle cell senescence and the underlying mechanisms.Methods:Fourteen apolipoprotein E-deficient(ApoE-/-)mice were used to establish an atherosclerosis model and were divided into two groups(n=7)using the random number method: a high-fat diet(HD)group and a high-fat diet plus 2-HOBA(1 mg/ml)(HD+ HOBA)group.Pulse wave velocity was used to assess vascular stiffness and a treadmill was used to assess exercise endurance.Oil Red O staining was used to detect the size and number of atherosclerotic plaques.Masson staining was used to detect the morphology of collagen fibers and elastic fibers in the plaque, the size of the necrotic core area of the plaque, and the thickness of the fibrous cap.Mouse smooth muscle cells were treated with different concentrations of 2-HOBA(100 μmol/L, 250 μmol/L and 500 μmol/L)to establish an H 2O 2-induced senescence model.Senescence-associated β-galactosidase staining was used to detect cell senescence.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression levels of senescence-related secretory phenotype factors, and Western blot was used to detect the expression levels of senescence-related signaling proteins. Results:Compared with the HD group, the HD+ HOBA group showed that the area and number of aortic atherosclerotic plaques were decreased, and the atherosclerotic plaques were stabilized.In addition, compared with the HD group, vascular stiffness in the HD+ 2-HOBA group decreased by 26%(2.59±0.32 mm/ms vs.3.50±0.28 mm/ms), with a statistically significant difference( P<0.01), and exercise endurance increased by 62%[(143.74±24.25)m vs.(233.50±30.21)m, P<0.01], suggesting that 2-HOBA was able to improve aortic vascular stiffness and exercise endurance in mice.2-HOBA ameliorated H 2O 2-induced vascular smooth muscle cell senescence and decreased the mRNA levels of H 2O 2-induced senescence-associated secretory phenotype factors such as interleukin-1β, interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1.Meanwhile, 2-HOBA also inhibited the expression of p53 and p21, the key signaling factors of senescence. Conclusions:2-HOBA suppresses the development and progression of atherosclerosis through inhibiting oxidative stress-related p53/p21 signaling activation and ameliorating vascular smooth muscle cell senescence and the aging-related inflammatory phenotype.
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Objective:To investigate the role and mechanisms of fibulin-1 in senescence-related calcification of rat vascular smooth muscle cells induced by high-concentrationphosphate treatment.Methods:From September 2020 to September 2021, rat primary vascular smooth muscle cells were extracted from the thoracic aorta and abdominal aorta of 10 male SD rats aged 6 to 8 weeks.Phosphate(2.5 mmol/L Pi)was used to stimulate the calcification of vascular smooth muscle cells(VSMCs)in a model of stress-induced senescence-related calcification.Cellular senescence was assessed by SA-β-gal staining.Cellular calcification was determined by alizarin red staining and quantification of calcium deposition.Phenotypic transformation indexes and the expression of fibulin-1 during the process of calcification were detected by Western blot.The expression of fibulin-1 in primary rat vascular smooth muscle cells was knocked down by siRNA, the expression of pSmad3 was detected by immunofluorescence, and the effects of fibulin-1 on phenotypic transformation indexes of smooth muscle cells were detected by Western blot.The cells were cultured with recombinant fibulin-1 while transforming growth factor beta(TGF-β)inhibitor A83-01 and pSmad3 inhibitor SIS3 were also added.The senescence and calcification indexes of smooth muscle cells were detected by Western blot.Results:In the stress-induced aging model with phosphate stimulation of calcification in rat VSMCs, the expression of fibulin-1 was up-regulated( t=11.20, P<0.01), the expressions of MHC and SM22α was down-regulated( t=7.97, P<0.01; t=10.27, P<0.01), and the expression of osteoblastic phenotype markers OPN and Bmp2 and senescence marker P53 was up-regulated( t=4.79, P<0.01; t=9.56, P<0.01; t=14.07, P<0.01). Knockdown of fibulin-1 attenuated the degree of senescence and calcium deposition in VSMCs( t=12.90, P<0.05)and decreased the expression of OPN, Bmp2 and P53( t=5.92, P<0.05; t=10.15, P<0.01; t=8.28, P<0.01), at the same time, and TGF-β and pSmad3 expression was inhibited( t=12.90, P<0.01; t=7.46, P<0.01). After the addition of TGF-β/ smad3 pathway inhibitors, the stimulatory effect of recombinant fibulin-1 on phenotypic transformation and senescence protein expression inVSMCs was significantly reduced( t=4.52, P<0.01; t=9.82, P<0.01; t=3.85, P<0.05). Conclusions:Fibulin-1 can promote aging-related calcification of vascular smooth muscle cells through the TGF-β/smad3 signaling pathway.
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Objective:To explore alterations of myocardial mechanics in mice models of physiological aging.Methods:Mice aged from 3 weeks to 24 months were chosen(n=50). Conventional echocardiography and layer speckle tracking echocardiography(LS-STE)were applied to evaluate alterations of myocardial mechanics in different ages(each for 10 mise). Pathological myocardial alterations in the aging process were detected using HE and Masson's trichrome staining.Results:Clear age-dependent changes in mice of different ages were observed when assessed using parameters of conventional echocardiography( P<0.05 for all). Values from parameters of LS-STE also showed that longitudinal, circumferential and radial strain in both the endocardium and the epicardium gradually decreased during physiological aging( P<0.05 for all). Compared with the 3-weeks old group, longitudinal strain in the endocardium was significantly reduced in the 14-months old group[(-23.49±2.32) vs.(-17.19±2.28), P<0.05]; Compared with the 3-weeks old group, radial strain, longitudinal strain in the endocardium, longitudinal strain in the epicardium, circumferential strain in the endocardium and circumferential strain in the epicardium were significantly reduced in the 24-months old group[(32.90±5.01) vs.(21.80±5.54), (-23.49±2.32) vs.(-15.44±2.27), (-13.23±3.19) vs.(-7.59±2.21), (-25.93±4.09) vs.(-20.31±4.08), (-9.30±1.92) vs.(-6.01±1.04), P<0.05)]; HE and Masson's trichrome staining of the myocardium indicated increases in the cross-sectional area of cardiomyocytes and fibrosis during the aging process. Conclusions:LS-STE can accurately detect early cardiac dysfunction and pathological myocardial alterations associated with aging in mice and may serve as an effective tool in evaluating anti-myocardial aging.
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Objective:To evaluate the effect of supervised high-intensity interval training(HIIT)on physical fitness of elderly patients with type 2 diabetes mellitus.Methods:In a prospective randomized controlled study, 47 elderly type 2 diabetes mellitus patients were randomized into either the HIIT group(n=24)or the control group(n=23). All HIIT sessions were conducted under supervision once every other day for 10 weeks.Each session included 40 cycles that consisted of high-intensity training(resting oxygen consumption + 80% oxygen consumption reserve)for 30 seconds and low-intensity training(resting oxygen consumption + 50% oxygen consumption reserve)for 30 seconds.Cardiopulmonary exercise testing, bioelectric impedance analysis and homeostasis model assessment-2(HOMA-2)were used for the measurement of physical fitness, body composition and insulin sensitivity(HOMA-2 IS)before and after intervention. Results:After 10 weeks, peak oxygen uptake(23.6±4.1 ml·kg -1·min -1vs.21.0±4.6 ml·kg -1·min -1, P<0.05), oxygen uptake at the anaerobic threshold(14.1±1.6 ml·kg -1·min -1vs.12.1±2.3 ml·kg -1·min -1, P<0.01), oxygen pulse at the anaerobic threshold(10.7±2.6 ml/min vs.(9.3±1.9)ml/min, P<0.05)and Ln(100·HOMA-2 IS)(4.6±0.4 vs.4.2±0.5, P<0.01)improved in the HIIT group more than in the control group.There were no significant differences in body composition between the two groups( P>0.05). After adjusting for age and body mass index, there was a linear correlation between peak oxygen uptake and Ln(100·HOMA-2 IS)at baseline( r=0.376, P<0.05), but not between changes in peak oxygen uptake and changes in Ln(100·HOMA-2 IS)( r= 0.05, P>0.05). Conclusions:Ten-week HIIT can improve physical fitness of elderly type 2 diabetes mellitus patients.The benefit comes not only from improvement of insulin sensitivity but also from enhancement of heart function.
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Objective:To analyze the composition and functional characteristics of the intestinal microflora in novel coronavirus pneumonia patients with arterial stiffness, in order to provide empirical evidence for rational use of intestinal microecological modulators.Methods:Patients with novel coronavirus pneumonia admitted to our hospital between April 5 and April 19, 2020 were enrolled as research subjects.They were divided into the stiffness group and the control group according to the results of arterial stiffness.Stool samples were collected within 7 days of admission.Intestinal flora DNA was analyzed and entered into a database, shotgun metagenomic sequencing was performed, and bioinformatics analysis was conducted based on sequencing results.Results:A total of 16 patients with novel coronavirus pneumonia were included in this study, including 7 in the stiffness group and 9 in the control group.Brachial-ankle pulse wave velocity and blood pressure were higher in the stiffness group than in the control group( P<0.05). Beta diversity analysis at the phylum level showed that there were significant differences in the composition of the intestinal flora between the two groups( P<0.05). Patients with arterial stiffness had a lower relative abundance than the controls in fecal Holdemanella, Mitsuokella, Deinococcus, Lachnospira, Turicibacter, Butyrivibrio, Sporomusa, and Halanaerobium, species associated with the production of short-chain fatty acids(SCFAs), regulation of energy metabolism, anti-radiation, anti-oxidative stress and anti-inflammatory effects.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that the intestinal flora in the control group was mainly involved in the pathways of lipopolysaccharide biosynthesis, metabolism of SCFA and other amino acids, and membrane transport, while the intestinal flora in the stiffness group was mostly concerned with the pathways of amino acid metabolism and DNA damage repair. Conclusions:The use of microbial agents capable of increasing short-chain fatty acids in patients with novel caronavirus infection may contribute to the restoration of intestinal flora homeostasis.
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The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit a typical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.
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Vascular aging refers to degenerative changes in vascular structure and function.Based on speckle-tracking echocardiography, velocity vector imaging can be used to comprehensively evaluate the mechanical characteristics and wall functions in the process of vascular aging and plays an important role in the early detection and treatment of vascular age-related diseases by accurately locating the vessels and three-dimensionally evaluating the velocity, strain and strain rate in different directions.In this article, the application of this technique in the evaluation of vascular aging and related diseases including hypertension, diabetes and atherosclerosis is described.
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The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.
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Objective To investigate the effects and mechanism of advanced glycosylation end products (AGEs)on endothelial cell senescence and endothelial barrier dysfunction.Methods Human umbilical vein endothelial cells (HUVECs)were isolated and cultured.The cells were randomized into three groups:the control group(normal medium),the bovine serum albumin-treated group(BSA control group)and AEGs group(treated with AEGs-BSA).Senescence of HUVECs were detected by senescence-associated β-galactosidase (SA-beta-Gal)staining.The mRNA and protein expressions of senescence-related genes of p53,p21 and p16 in each group were determined by reverse transcription and real-time PCR(RT-qPCR)and Western blot.Reactive oxygen species(ROS)level was determined by dichlorodihdrofluorescence diacetate (DCFH-DA).The transendothelial electric resistance(TER)were measured by endothelial electric resistance meter.The protein levels of myosin light chain kinase (MLCK),phosphorylated myosin light chain (p-MLC),myosin light chain (MLC)were detected by Western blot.Results Compared with the control group and the BSA control group,the AGEs group showed the significantly increased positive rate of senescence-associated SA-beta-Gal staining (67.30 ± 0.75 ％ vs.7.81 ±0.35 ％ and 7.64 ± 0.91％,respectively,P ＜ 0.01)and the expressions of aging-related genes of p53,p21 and p16 were significantly increased (P ＜ 0.05)There was no significant difference in transendothelial electric resistance(TER)between the control group and theBSAgroup(48.0±6.3 Ω· cm2 vs.42.0±7.8 Ω· cm2,P＞0.05),while TER was lower in the AEGs group than in control group and the BSA group[(27.0±4.2)Ω · cm2 vs.(48.0±6.3)Ω · cm2 and (42.0 ± 7.8) Ω · cm2,P ＜0.01].ROS production had no significant difference between the control group and the BSA group[(38.36 ± 8.55) ％ vs.(41.67 ± 6.93) ％,p ＞ 0.05],while was increased in the AEGs group versus control group and the BSA group[(69.31±8.47)％ vs.(38.36±8.55) ％ and (41.67 ± 6.93) ％,P ＜0.05).The protein expression levels of MLK and p-MLC/MLC were higher in the AGEs group than in the control group and the BSA group(P＜0.05).Conclusions AGEs may lead to endothelial cell senescence and endothelial barrier dysfunction by promoting ROS production and oxidative stress,and by regulating MLCK signaling pathway.
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Objective To investigate the unusual drug-induced International Normalized Ratio(INR) change in elderly patients with warfarin treatment and its related mechanism. Methods A retrospective analysis was performed in 41 cases of elderly patients with unusual drug-induced INR change from 2011 to 2015 in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology. Results INR was increased unusually in 37 cases(90.2%) and was decreased unusually in 4 cases(9.8%).Intravenous drugs(80.5%) were prone to cause unusual INR change.Prostaglandin,antifungal drugs,antiarrhythmic drugs and lipid soluble vitamins were the commonly used drugs that induced adverse reaction,accounting for 26.8%,29.3%,29.3% and 9.8%,respectively. Conclusion Unusual drug-induced INR change is not rare in elderly patients with warfarin treatment during hospitalization.When other drugs are prescribed,INR should be measured more frequently and the dose of warfarin should be adjusted promptly.
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The clinical teaching of geriatrics is difficult to arouse the students' interest. The flipped classroom teaching method can improve it through the interaction. We used WeChat as a platform for flipped classes and designed a variety of micro lessons. The participation and study interests of students were obvi-ously increased through exchanging teaching, answering questions and discussing. The teaching efficiency was also improved after strengthening practice. The preliminary practice shows that this teaching method can provide students a virtual teaching platform. It not only can enhance the teaching effect, but also can share teaching resources in network even for the long-term cross hospital and cross school exchange promotion.
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Objective To investigate the diagnosis,treatment and prognosis of bilateral renal clear cell carcinoma in the elderly.Methods Clinical data from 38 cases of elder patients admitted with bilateral renal clear cell carcinoma in our department from 2010 to 2014 were retrospectively analyzed.Among the total 38 cases diagnosed by B ultrasound and CT,13 cases(A group)were treated with laparoscopic radical nephrectomy on one side,combined with microwave ablation on the other side;another 25 cases(B group)were treated with microwave ablation on bilateral sides.Patients were followed up for 24-36 months,with regularly checking by B ultrasound,CT and renal function.Results The operations were successful in total 38 cases (A +-B group),and no postoperative complications were found.All cases were diagnosed as pathologically proven bilateral renal clear cell carcinoma.Postoperative renal functions of the cases were decreased at different degrees as compared with preoperative renal functions,but not needing dialysis treatment.The microwave ablation on bilateral sides(B Group) versus A Group,significantly decreased the surgical time cost (P =0.012) and hospital stay(P =0.021).For both A and B group,postoperative renal function were declined in different degree.The damage extents of blood urea nitrogen,creatinine and creatinine clearance rate were less in group B than in group A at one week after surgery(P=0.008,0.009 and 0.006).Atpostoperative follow-up for 3 month,it was found that the damage extents of blood urea nitrogen,creatinine and creatinine clearance rate were less in group B than in group A (P =0.037,0.020 and 0.018).At postoperative follow-up for 30 months in average,no local recurrence or metastasis was found.Diagnosis of bilateral kidney clear cell carcinoma in the elderly mainly depended on B ultrasound,CT scan and MRI imaging.Conclusions As to the treatment of elderly patients with early renal clear cell carcinoma,considering both the general healthy condition of patients and tumor therapy and choosing microwave ablation might be good for efficiency and prognoses.
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Objective To investigate the efficacy and safety of perioperative use of different hemostatic drugs in elderly patients undergoing transurethral resection of the prostate (TURP).Methods A total of 480 elderly patients with benign prostatic hyperplasia (BPH) admitted to the Departments of Urology and Gerontology of our hospital from January 2010 to October 2014 were selected and randomly divided into 6 groups (n =80,each).Patients in all groups were given preoperative oral finasteride for 1 week,with each of the non-control groups receiving perioperative heamocoagulase agkistrodon,mangabeys hemocoagulase,reptilase,ethylenediamine diaceturate,or dicynone + paraaminomethyl benzoic acid (PAMBA).Intraoperative bleeding,perioperative hematocrit,hemoglobin change,continuous bladder irrigation time,adverse reactions and other clinical parameters were recorded.Results Operations went smoothly with all patients.Changes in perioperative blood routine indexes,coagulation function,intraoperative bleeding volume and continuous bladder irrigation time had significant differences between the control group and the groups treated with hemostatic drugs (all P＜0.05).No significant differences in perioperative blood routine indexes,coagulation function,intraoperative bleeding volume and continuous bladder irrigation time were found between groups treated with heamocoagulase agkistrodon,mangabeys hemocoagulase and reptilase,or between groups treated with ethylenediamine diaceturate and dicynone+PAMBA (all P＞ 0.05).There were significant differences in the perioperative blood routine indexes,coagulation function,intraoperative bleeding volume and continuous bladder irrigation time between the groups with and without blood coagulation enzymes (all P ＜0.05).Fibrinolytic responses occurred in 2 patients in the heamocoagulase agkistrodon group and were mitigated after drug withdrawal and fibrinogen infusion.Conclusions A reasonable perioperative dose of a hemostatic drug has good clinical effects in elderly patients undergoing TURP.Hemostatic drugs such as blood coagulation enzymes have certain advantages including safety over other types of hemostatic drugs,but their doses should not be too large.
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Case teaching method has been widely used in clinical medicine teaching.Because of the complicated diseases in elderly patients and the individual differences,it is difficult to achieve the goal of teaching only through several cases.Typical cases of different level are selected according to students' different learning stages and difficulty degree in longitudinal stepped case teaching.The students can gradually understand and master the theoretical knowledge through this method.In addition,their clinical thinking and the ability of solving practical problems can also be trained continuously.Preliminary practice shows that this teaching method is more suitable for the development of modern medical education and the needs of teaching.
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Objective To assess the association between helicobacter pylori (HP) infection and dyslipidemia in different gender population.Methods We conducted cross-sectional analysis using data of 1921 cases of demographic characteristics,anthropometry,life style,lipid profile,etc.,from the subjects who received health examination from January 2010 to June 2012 in Department of Geriatrics,Tongji Hospital.Diagnosis of HP infection was achieved by using 14C-Urea Breath Test (14C-UBT).The participants were divided into HP infection positive group and HP infection negative group by 14C-UBT.Results In female subjects,the levels of total cholesterol/high-density lipoprotein cholesterol (TC/HDL-c) were higher in HP positive group than HP negative group (P ＜ 0.05),but there was no obvious difference between the levels of low density lipoprotein cholesterol (LDL-c) in HP positive group and HP negative group.However,in the male subjects,the levels of LDL-c and TC/HDL-c were significantly increased in HP positive group than HP negative group (P ＜ 0.05).HP positive group had a greater risk for high TC/HDL-c both in female and male subjects.In female subjects,the risk for high TC/HDL-c in HP positive group was 1.90 times of that in HP negative group (95％ CI,1.06 ～ 3.38).In male subjects,the risk for high TC/HDLc in HP positive group was 1.56 times of that in HP negative group (95％ CI,1.21 ～ 2.00).But only in male subjects,the risk for high LDL-c in HP positive group was 2.33 times of that in HP negative group (95 ％ CI,1.34 ～ 4.06).Conclusions We observed that HP infection was probability associated with dyslipidemia.
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OBJECTlVE To investigate the mechanism of verapamiI in the treatment of type 2 Iong QT syndrome(LQT2)using a rabbit Ieft ventricuIar myocardiaI wedge preparation. METHODS E-4031 (0.5 μmoI·L-1 )was used to induce the LQT2 modeI after rabbit Ieft ventricuIar wedge preparations were equiIibrated for 1 h,and verapamiI(0.5,1.0 and 2.5 μmoI·L-1 ,respectiveIy)was perfused in different groups. Data were coIIected for a period of 30 min starting 30 min after adding the respective drug. Transmembrane action potentiaIs of endocardiaI and epicardiaI myocardium were recorded simuItaneous-Iy at a basic cycIe Iength of 2000 ms(S1S1)together with a transmuraI ECG. The effect of verapamiI (0.5,1.0 and 2.5 μmoI·L-1 )on action potentiaI duration at 90% repoIarization(APD90 ),QT intervaI, transmuraI dispersion of repoIarization(TDR)and the deveIopment of earIy afterdepoIarization(EAD) and torsades de pointes(TdP)were evaIuated in the LQT2 myocardiaI wedge modeI. RESULTS E-4031 (0.5 μmoI·L-1 )markedIy proIonged endocardiaI and epicardiaI APD90 and QT intervaI( P﹤0.01),and dramaticaIIy increased TDR(P﹤0.01). Spontaneous or programmed eIectricaI stimuIation-induced EAD and TdP were aIso observed in the modeI. VerapamiI(0.5,1.0 and 2.5 μmoI·L-1 )dose-dependentIy abbreviated endocardiaI and epicardiaI APD90 and QT intervaI(P﹤0.01),significantIy decreased TDR(P﹤0.01),and suppressed EAD and TdP in the LQT2 modeI. Concordant but stronger effects on the eIectro-physioIogicaI properties of the LQT2 modeI were noticed when nifedipine was perfused. CONCLUSlON VerapamiI inhibits TdP in the LQT2 modeI by reducing TDR and suppressing EAD.
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Objective To explore the risk factors of prehypertension and the relationship between blood pressure and atherosclerosis.Methods The data of 456 cases in the Department of General Medicine were cross-sectional analyzed,including 174 subjects with normotension and 282 with prehypertension.The information was consisted of demographic characteristics,blood pressure,blood biochemical metabolism index,brachia-ankle pulse wave velocity (baPWV),ankle-brachial index (ABI) and carotid intima media thickness (CIMT).Results Compared to normotension group,the levels of systolic pressure,diastolic pressure,pulse pressure,body mass index,fasting blood glucose,glycosylated hemoglobin,triglyceride,uric acid,and C-reactive protein in prehypertension group were significantly increased (P ＜ 0.05) ; and high-density lipoprotein cholesterol was significantly decreased (P ＜0.05) ; the body mass index(OR =1.185),triglyceride(OR =1.302),and fasting blood sugar (OR =1.690) were the independent risk factors of prehypertension ; baPWV and CIMT in prehypertension group were higher,but ABI and artery atheromatous plaque rate were not obvious changed.When baPWV or CIMT were set as the dependent variables,multiple linear regression analysis showed that systolic blood pressure(β =0.226,P =0.007),fasting blood glucose(β =0.209,P =0.018),and age(β =0.279,P =0.002) were risk factors of baPWV;systolic blood pressure(β =0.118,P =0.015),body mass index(β =0.109,P =0.001),and age(β =0.396,P =0.001) were risk factors of CIMT.Conclusions Body mass index,triglycerides,and fasting blood sugar were the independent risk factors of prehypertension.The early subclinical damage of hardening of the arteries was occurred in the prehypertension cases,and systolic blood pressure was closely related with baPWV or CIMT.
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Cardiac hypertrophy is an independent risk factor for sudden cardiac death in clinical settings and the incidence of sudden cardiac death and ventricular arrhythmias are closely related. The aim of this study was to determine the effects of the calmodulin-dependent protein kinase (CaMK) II inhibitor, KN-93, on L-type calcium current (I(Ca, L)) and early after-depolarizations (EADs) in hypertrophic cardiomyocytes. A rabbit model of myocardial hypertrophy was constructed through abdominal aortic coarctation (LVH group). The control group (sham group) received a sham operation, in which the abdominal aortic was dissected but not coarcted. Eight weeks later, the degree of left ventricular hypertrophy (LVH) was evaluated using echocardiography. Individual cardiomyocyte was isolated through collagenase digestion. Action potentials (APs) and I(Ca, L) were recorded using the perforated patch clamp technique. APs were recorded under current clamp conditions and I(Ca, L) was recorded under voltage clamp conditions. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were observed under the conditions of low potassium (2 mmol/L), low magnesium (0.25 mmol/L) Tyrode's solution perfusion, and slow frequency (0.25-0.5 Hz) electrical stimulation. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were also evaluated after treatment with different concentrations of KN-92 (KN-92 group) and KN-93 (KN-93 group). Eight weeks later, the model was successfully established. Under the conditions of low potassium, low magnesium Tyrode's solution perfusion, and slow frequency electrical stimulation, the incidence of EADs was 0/12, 11/12, 10/12, and 5/12 in sham group, LVH group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. At 0 mV, the current density was 6.7±1.0 and 6.3±0.7 PA·PF(-1) in LVH group and sham group, respectively (P>0.05, n=12). When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)% in the hypertrophic cardiomyocytes of the two groups, respectively (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) values were lowered by (13.4±3.7)% and (40±4.9)%, respectively (P<0.01, n=12). KN-93, a specific inhibitor of CaMKII, can effectively inhibit the occurrence of EADs in hypertrophic cardiomyocytes partially by suppressing I(Ca, L), which may be the main action mechanism of KN-93 antagonizing the occurrence of ventricular arrhythmias in hypertrophic myocardium.