ABSTRACT
<p><b>BACKGROUND</b>Catestatin, a chromogranin A-derived peptide, is a potent antagonist of nicotine-evoked catecholamine release. We know that catecholamine plays an important role in cardiovascular remodeling induced by hypertension, therefore we hypothesized that catestatin would affect target-organ structure during hypertension.</p><p><b>METHODS</b>Twelve spontaneously hypertensive rats (SHRs) were randomized to SHR control group and catestatin group, the normal control group was comprised of six healthy Wistar-Kyoto rats of the same age. Tail-cuff blood pressure and pulse rate were obtained at weeks 1, 4 and 8. At the end of the eight-week period, the heart, abdominal aorta and left kidney were excised and weighed, VG staining was done and the intima-media thickness of vessels and the collagen volume fraction were assessed by an image acquisition and analysis system. The proliferating cell nuclear antigen (PCNA) was observed by immunohistochemistry, and real time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of proliferative genes including cyclin A, ki67 and PCNA in the abdominal aorta.</p><p><b>RESULTS</b>All the parameters in SHR observed in the present study increased significantly compared to Wistar Kyoto rats (P < 0.01). With intervention with catestatin, the systolic blood pressure decreased slightly but it was not significantly different from the SHR control, the cardiac mass index and left ventricular mass index both decreased significant ly, the collagen volume fraction decreased by nearly 30% in the heart, by 25% in vessels and by 10% in the kidney, and the intima-media thickness and expression of proliferative genes, including cyclin A, ki67 and PCNA, in the abdominal aorta also decreased significant ly.</p><p><b>CONCLUSIONS</b>The present study indicated that catestatin could ameliorate proliferating changes of heart, kidney and vessels during hypertension, especially to the deposition of interstitial collagen. Blood pressure was not the main factor to mediate this effect, which suggested that catestatin could become a novel protective factor for hypertensive target organs.</p>
Subject(s)
Animals , Male , Rats , Aorta, Abdominal , Pathology , Blood Pressure , Cell Proliferation , Chromogranin A , Pharmacology , Heart Rate , Hypertension , Drug Therapy , Pathology , Kidney , Pathology , Peptide Fragments , Pharmacology , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
<p><b>OBJECTIVE</b>To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype.</p><p><b>METHODS</b>Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms.</p><p><b>RESULTS</b>Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype.</p><p><b>CONCLUSIONS</b>Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.</p>
Subject(s)
Humans , Asian People , Cardiomyopathy, Hypertrophic , Genetics , Case-Control Studies , Exons , Genotype , Mutation , Mutation, Missense , Pedigree , Phenotype , Polymorphism, Genetic , Troponin T , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients.</p><p><b>CONCLUSION</b>MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Asian People , Genetics , Cardiomyopathy, Hypertrophic , Genetics , Carrier Proteins , Genetics , DNA Mutational Analysis , Exons , Genotype , Mutation , Phenotype , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>The present study was designed to observe the plasma concentrations of hydrogen sulfide (H(2)S) and homocysteine (HCY) in hypertensive patients with different blood pressure levels and complications.</p><p><b>METHODS</b>A total of 165 outpatients with essential hypertension were involved in this study (84 males, 81 females, mean age 59.81 +/- 10.60 years old). There were 28 new-onset untreated, 137 ever-treated patients. Among ever-treated patients, blood pressure was normal in 38, grade 1 hypertension in 43, grade 2 and 3 hypertension in 56 patients. Thirty-two patients were accompanied with coronary heart disease (CAD), and 42 patients were accompanied with stroke. A total of 32 age- and sex-matched healthy controls (18 males) were also recruited. Plasma H(2)S and HCY concentrations were determined in all patients and controls.</p><p><b>RESULTS</b>(1) Plasma H(2)S levels were significantly lower (P < 0.05) and HCY levels were significantly higher (P < 0.01) in ever-treated hypertensive patients compared with controls. (2) Plasma HCY levels were significantly higher in patients with hypertension history > 6 months and complicated with CAD compared to patients without CAD. (3) Plasma H(2)S concentrations in patients with stroke history > 5 years were significantly lower than that in patients without stroke (P < 0.01). Plasma HCY concentrations were increased in proportion to stroke history. (4) In ever-treated hypertensive patients, plasma H(2)S concentrations in patients with grade 2 and 3 hypertension were significantly lower (P < 0.05) and HCY levels significantly higher (P < 0.01) than that in patients with well-controlled blood pressure.</p><p><b>CONCLUSION</b>Hyperhomocysteinemia and the novel signaling gasotransmitter H(2)S might play important roles in the pathogenesis and development of hypertension.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blood Pressure , Case-Control Studies , Gases , Blood , Homocysteine , Blood , Hydrogen Sulfide , Blood , Hypertension , Blood , Plasma , ChemistryABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.</p><p><b>RESULTS</b>Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.</p><p><b>CONCLUSIONS</b>Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Asian People , Genetics , Cardiac Myosins , Genetics , Cardiomyopathy, Hypertrophic, Familial , Ethnology , Genetics , Carrier Proteins , Genetics , Mutation , Myosin Heavy Chains , Genetics , Pedigree , Phenotype , Troponin T , GeneticsABSTRACT
<p><b>OBJECTIVES</b>To investigate the efficacy of intracoronary transfer of autologous bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction (MI) on left ventricular function and myocardial perfusion.</p><p><b>METHODS</b>Thirty-five patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled study (20 patients in cell transplantation group; 15 patients in control group). All patients were treated by standard drug therapy and percutaneous coronary intervention (PCI). Baseline and 3 months follow-up evaluations included complete clinical and laboratory examinations, six minutes walk test, echocardiography, Dual-isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) and cardiac magnetic resonance imaging (MRI).</p><p><b>RESULTS</b>Baseline parameters were similar between the two groups. NYHA classification and six minutes walk test at 3 months follow-up were also similar between the two groups. However, left ventricular ejection fraction (LVEF) determined by echocardiography and DISA-SPECT was significantly higher; regional wall motion measured by echocardiography and cardiac MRI, myocardial viability and myocardial perfusion in the infarct zone assessed by DISA-SPECT were all significantly improved than before transplantation and than that in control group at 3 months follow-up.</p><p><b>CONCLUSIONS</b>Our results indicate that intracoronary transplantation of ABMMNCs could improve the left ventricular systolic function and beneficially affect myocardial perfusion up to 3 months post transplantation in patients with myocardial infarction.</p>
Subject(s)
Humans , Bone Marrow Transplantation , Methods , Follow-Up Studies , Myocardial Infarction , General Surgery , Therapeutics , Prospective Studies , Tomography, Emission-Computed, Single-Photon , Transplantation, Autologous , Ventricular Function, LeftABSTRACT
Objective To explore the relationship between size,shape and function of the left atrium appendage (LAA) and its thrombosis in patients with atrial fibrillation (AF) by transesophageal echocardiography (TEE) to provide evidence for clinical risk assessment,prognosis evaluation and treatment guidance.Method Length,diameter,end-diastolic volume (EDV) and ejection velocity (PEV) of LAA were measured in 41 patients with AF,and thrombus in LAA was detected by TEE.Results Thrombus in LAA was detected in seven of 41 patients of AF (17%).No significant difference in size and EDV was found between the patients with and without thrombus,but there was significant difference in PEV between them (P