Performance at altitude and angiotensin I-converting enzyme genotype

The insertion (I) rather than deletion (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study—an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.     

Association of essential hypertension in elderly Japanese with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene

Recent evidence suggests that an insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) is associated with myocardial infarction and related cardiovascular diseases. We investigated a possible association of the ACE polymorphism with essential hypertension in a total of 263 cases/controls from among the elderly (age, over 70 years) and middle-aged (age between 30 and 60 years) Japanese population. The frequency of the I/I homozygote was significantly higher in hypertensive subjects than in controls in the elderly age group (33/57 vs 16/46; P = 0.02), but no association was observed in the middle-aged group (25/75 vs 26/85; P = 0.71). Similarly, having at least one insertion allele was associated with essential hypertension in the elderly age group (83/114 vs 46/92 in controls; P = 0.001), but not in the middle-aged group (78/150 vs 94/170; P = 0.524). These data suggest that genetic variation at the ACE locus may be associated with some determinants for blood pressure in elderly persons, and imply the involvement of the ACE insertion/deletion polymorphism in the etiology of age-related essential hypertension in the Japanese population. Received: April 18, 2000 / Accepted: July 25, 2000     

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

OBJECTIVE:

The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension.

METHODS:

A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies.

RESULTS:

The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively).

CONCLUSIONS:

The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension.     

The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACE genotype

The deletion (D) rather than insertion (I) allele of the angiotensin-converting enzyme (ACE) gene is associated with greater ACE activity. We examined: (1) the influence of posture change (recumbent to seated) and acute exercise on serum ACE and angiotensin II (Ang II) activity; (2) the relationship between ACE and Ang II levels; and (3) the influence of ACE genotype on changes in ACE and Ang II levels with posture and exercise. Recreationally active young male Caucasians (10 each of II, ID and DD genotypes) rested for 35 min supine then 15 min upright, took 20 min bicycle ergometric exercise at 70% maximum oxygen uptake, then rested for 40 min. Samples were taken throughout for ACE activity and Ang II levels. Supine ACE levels were dependent upon ACE genotype [24.8 (5.7), 26.9 (4.5), 45.5 (6.4) nmol His-Leu ml^–1 min^–1; II, ID, DD, respectively; P<0.00005] and thereafter. ACE activity rose with assumption of a seated posture [from 32.4 (10.9) nmol His-Leu ml^–1 min^–1 to 35.0 (11.5) nmol His-Leu ml^–1 min^–1, P<0.00001], the absolute rise being independent of genotype [3.22 (1.92), 1.6 (1.6), 2.4 (2.3) nmol His-Leu ml^–1 min^–1; II, ID, DD; P=0.22], unlike percentage change [12.8 (6.8), 5.6 (5.5), 5.3 (5.0)%; II, ID, DD; P<0.01, and P=0.004 for II vs presence of the D allele]. A further genotype-independent rise occurred with exercise [+2.9 (3.7) units, P<0.0003]. An associated rise in Ang II levels [30.3 (15.9), or 2587.9 (489.76)%, P<0.00001] was independent of ACE genotype or activity. Upright posture increases ACE activity, and this may be influenced by ACE genotype. ACE activity and Ang II levels rise independently with exercise in a non-genotype-dependent fashion.     

心房颤动患者心房纤维化与缝隙连接重构的关系

目的：探讨心房颤动患者心房肌胶原纤维与缝隙连接重构在房颤发病机制中的可能作用以及它们之间的关系。 方法： 取44例心脏病患者的右心耳标本（房颤26例,为AF组；窦性心律18例，为SR组）,（1）行天狼猩红染色，偏光显微镜下观察AF组与SR组心房肌Ⅰ型胶原并通过图像分析系统分析统计2组间Ⅰ型胶原含量分数（collagen volume fraction of collagen Ⅰ,CVF-Ⅰ）的差异；（2）超微病理切片，透射电镜下观察闰盘并统计闰盘组数及闰盘重构分数（remodeled intercalated disc fraction, RIDF）；（3）连接蛋白43（connexin 43,Cx43）免疫组化染色，普通显微镜下观察分析缝隙连接蛋白Cx43的含量分数（volume fraction of Cx43,Cx43VF），统计2组间的差异；（4）CVF-I与Cx43VF、RIDF分别进行Pearson相关分析。 结果： （1）AF组CVF-I高于SR组（1.26 vs 0.57, P＜0.01）；(2)2组间闰盘组数无显著差异(9.54 vs 10.11, P>0.05), AF组闰盘重构分数大于SR组(39.48 vs 15.61, P＜0.01)；(3)AF组Cx43VF低于SR组(3.45 vs 5.22, P＜0.01)；(4)CVF-I与闰盘重构比例正相关(r＝0.96,P＜0.01)；(5)CVF-I与Cx43VF负相关(r＝－0.98,P＜0.01)。 结论： 房颤患者Ⅰ型胶原纤维化程度增加，闰盘与连接蛋白发生重构。纤维化可能分离心肌，使闰盘重构,进而影响到缝隙连接蛋白的分布，参与房颤发生发展的过程。     

Association of a G994 --> T (Val279 --> Phe) polymorphism of the plasma platelet-activating factor acetylhydrolase gene with myocardial damage in Japanese patients with nonfamilial hypertrophic cardiomyopathy

Plasma platelet-activating factor acetylhydrolase (PAF-AH) acts as a key defense against oxidative stress by hydrolyzing PAF and oxidized phospholipids. Deficiency of the activity of this enzyme may thus potentially result in predisposition to myocardial damage. The possible role of the G⁹⁹⁴ (V allele) → T (F allele) polymorphism of the PAF-AH gene in modulating cardiac function was investigated in 142 Japanese subjects with nonfamilial hypertrophic cardiomyopathy (HCM). Logistic regression analysis adjusted for age, sex, height, and body weight revealed that the frequency of the F allele was significantly higher in HCM patients than in 284 healthy controls. Echocardiographic examination revealed that left ventricular (LV) end-diastolic and end-systolic dimensions were significantly greater in HCM patients with the FF genotype than in those with the VV genotype. Cardiac catheterization revealed that LV end-diastolic pressure was significantly higher, whereas the LV ejection fraction was significantly smaller, for HCM patients with the F allele than for those with the VV genotype. Interstitial fibrosis was significantly more severe in HCM subjects with the FF genotype than in those with the VV genotype. These results suggest that the G⁹⁹⁴→ T (Val²⁷⁹→ Phe) polymorphism in the plasma PAF-AH gene may exacerbate cardiac damage in Japanese individuals with nonfamilial HCM, although this polymorphism is unlikely to be a causative factor for this condition. Received: February 26, 2001 / Accepted: April 21, 2001     

芳香烃受体在心房颤动患者心房组织中的表达及意义

目的:检测芳香烃受体(AhR)在风湿性心脏病(风心病)心房颤动患者右心耳组织中的表达,探讨其在心房纤维化中的作用及意义。方法:取风心病换瓣手术患者的右心耳组织为实验组,其中风心病窦性心律组25例和风心病慢性房颤组11例;取先天性心脏病(先心病)心脏手术患者的右心耳组织12例作为对照组。采用Masson染色法检测右心耳组织胶原含量,采用免疫组化技术检测AhR、AhR核转位蛋白(ARNT)和CYP1A1蛋白的表达和分布,采用实时荧光定量PCR检测AhR、ARNT和CYP1A1的mRNA表达,采用Western blot检测AhR、ARNT和CYP1A1的蛋白表达。结果:与先心病组相比,风心病窦律组和风心病慢性房颤组胶原含量和AhR、ARNT、CYP1A1的表达明显增高;与风心病窦律组相比,风心病慢性房颤组胶原含量和AhR、ARNT、CYP1A1的表达明显增高(P0.05)。结论:风心病患者心房组织中AhR的表达与纤维化程度相关;AhR/ARNT/CYP1A1在风心病患者中表达增加,可能参与风心病心房纤维化的发生发展。     

Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

OBJECTIVE:

Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy.

METHODS:

Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m²) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%).

RESULTS:

Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47–13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43–20.12; p = 0.013].

CONCLUSION:

Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.     

Effects of the new angiotensin-converting enzyme inhibitor,ramipril, in patients with essential hypertension

Summary The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1–2 h of the first dose; the maximum decrease was reached at 4–6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.Abbreviations ACE angiotensin converting enzyme - PRA plasma renin activity     

螺内酯对高甲状腺素诱导的兔心房颤动和心房重构的影响

目的:探讨螺内酯对高甲状腺素诱导的兔心房颤动(AF)和心房重构的影响。方法:新西兰兔33只随机分为3组:正常对照组(C)、高甲状腺素组(H)和螺内酯组(S)。H和S组腹腔注射甲状腺素4周建立兔甲亢性AF模型,之后,S组给予螺内酯灌胃2周。给药结束后,通过心内电生理高频刺激诱发AF,计算AF诱发率,测量心房有效不应期(AERP)。荧光定量PCR测定L型钙通道亚基(Cav1.2)、钾通道相关亚基(Kv1.5、Kv4.3)和缝隙连接蛋白(Cx40、Cx43)的mRNA表达,Western blot和免疫组化测定上述指标的蛋白表达。结果:螺内酯降低AF诱发率。H组和S组的AERP无明显差异(P0.05)。S组Cav1.2蛋白表达水平明显高于H组(P0.05)。S组Kv1.5的mRNA和蛋白表达水平均明显低于H组(P0.05),S组Kv4.3的蛋白表达水平显著低于H组(P0.05)。S组Cx43的mRNA表达水平明显低于H组(P0.01),S组Cx40的蛋白表达水平显著低于H组(P0.05)。结论:螺内酯可降低高甲状腺素所致的AF诱发率,改善其引起的心房重构。     

心房颤动患者心房Ⅰ型胶原重构与左心房扩大

目的：探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12 例,为房颤组；窦性心律12 例，为窦律组)。（1）HE染色，观察房颤组与窦律组心肌纤维以及细胞核、细胞外基质的差异。（2）免疫组化染色，在普通显微镜下观察窦律组与房颤组心房Ⅰ型胶原并使用图像分析系统分析2组的胶原含量分数（collagen volume fraction, CVF），统计2组间Ⅰ型胶原含量分数（CVF-Ⅰ）的差异。（3）〖JP+1〗对CVF-I与左房直径进行Pearson相关分析。结果:(1)房颤组CVF-Ⅰ高于窦律组(CVF-I: 9.29 ±0.85 vs 6.90±1.47, P<0.01)；（2）房颤组心房大于窦律组（6.16±1.01 vs 4.47±0.99， P<0.01）；（3）心房大小与Ⅰ型胶原含量不存在相关性（r=0.33, P>0.05）。 结论:房颤患者的心房纤维化程度增加、左心房扩大，纤维化与左房扩大可能通过一定的途径，直接或间接参与了房颤的发病过程。     

Regional left atrial interstitial remodeling in patients with chronic atrial fibrillation undergoing mitral-valve surgery

Ablation of the left atrial free wall around the pulmonary vein ostia (LAFW) may be effective in the treatment of chronic atrial fibrillation associated with mitral disease (CAF-MVD). Using light and conventional electron microscopy analyses, we wanted to evaluate, in CAF-MVD, the interstitial remodeling in the LAFW as well as in a more remote region, such as the left atrial appendage (LAA). LAFW and LAA samples were obtained from 33 CAF-MVD patients during combined mitral surgery and radiofrequency ablation and from 16 autoptic controls. Interstitial fibrosis (IF) and perivascular fibrosis (PF), capillary densities and the maximal oxygen diffusion distance were morphometrically determined. In CAF-MVD patients, the LAFW, compared with the LAA, showed a higher percentage of IF (7.16±3.23% versus 2.51±1.40%, respectively), a lower myocardial capillary density per mm² (830±106 versus 989±173) and an increased oxygen maximal diffusion distance (19.70±1.27 m versus 18.13±1.58 m). All these values were also significantly different than controls. No differences were found in evaluating PF. At variance with the LAA, in CAF-MVD patients, the LAFW around the pulmonary vein ostia is a region characterized by a marked interstitial remodeling such that it may be morphologically indicated as an appropriate target for ablation treatment aimed at sinus rhythm restoration.     

Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac disease and manifests predominantly as left ventricular hypertrophy. Mutations in the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease in about 30% of cases where mutations were identified. We clinically evaluated a large group of 147 consecutive HCM patients from three cardiology centers in Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the patients was systematically analyzed in the whole coding region of the MYH7 gene using PCR, single-strand conformation polymorphism analysis, and automated sequencing. Eleven different missense mutations (including seven novel ones) in 11 unrelated patients were identified, showing a mutation frequency of 7.5% in the study population. We further examined the families of five patients (three of German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We observed a clear, age-dependent penetrance with onset of disease symptoms in the fourth decade of life. Genotype–phenotype correlations were different for each mutation, whereas the majority was associated with an intermediate/malign phenotype. In conclusion, we report a systematic molecular screening of the complete MYH7 gene in a large group of consecutive HCM patients, leading to a genetic diagnosis in 38 individuals. Information about the genotype in an individual from one family could be very useful for the clinician, especially when dealing with healthy relatives in doubt of their risk about developing HCM. The increasing application of genetic screening and the increasing knowledge about genotype–phenotype correlations will hopefully lead to an improved clinical management of HCM patients.An erratum to this article can be found at Andreas Perrot and Hajo Schmidt-Traub contributed equally to this work     

Early experience using a left atrial appendage occlusion device in patients with atrial fibrillation

Purpose

Atrial fibrillation (AF) is one of the major risk factors for ischemic stroke, and 90% of thromboembolisms in these patients arise from the left atrial appendage (LAA). Recently, it has been documented that an LAA occlusion device (OD) is not inferior to warfarin therapy, and that it reduces mortality and risk of stroke in patients with AF.

Materials and Methods

We implanted LAA-ODs in 5 Korean patients (all male, 59.8±7.3 years old) with long-standing persistent AF or permanent AF via a percutaneous trans-septal approach.

Results

1) The major reasons for LAA-OD implantation were high risk of recurrent stroke (80%), labile international neutralizing ratio with hemorrhage (60%), and 3/5 (60%) patients had a past history of failed cardioversion for rhythm control. 2) The mean LA size was 51.3±5.0 mm and LAA size was 25.1×30.1 mm. We implanted the LAA-OD (28.8±3.4 mm device) successfully in all 5 patients with no complications. 3) After eight weeks of anticoagulation, all patients switched from warfarin to anti-platelet agent after confirmation of successful LAA occlusion by trans-esophageal echocardiography.

Conclusion

We report on our early experience with LAA-OD deployment in patients with 1) persistent or permanent AF who cannot tolerate anticoagulation despite significant risk of ischemic stroke, or 2) recurrent stroke in patients who are unable to maintain sinus rhythm.     

Overview of oral antithrombotic treatment in elderly patients with atrial fibrillation

Atrial fibrillation (AF) is an age-related arrhythmia, particularly affecting elderly patients. The ultimate goals in the treatment of AF are to improve prognosis and quality of life. Anticoagulants are effective for stroke prevention in AF patients, however, managing anticoagulation in elderly patients is especially challenging; requiring a comprehensive assessment of the patient and deep understanding of available therapies and doses to maximize the net benefit. This review summarizes available evidence on the efficacy and safety of anticoagulation therapy, and provides contemporary updates on the management of elderly patients with AF.     

Changes in angiotensin-converting enzyme activity and angiotensin I level in asthmatic and healthy children after submaximal physical work

The changes in angiotensin-converting enzyme activity and serum angiotensin I levels have been studied in 16 controls subjected to submaximal physical work. Baseline (Pre-exercise) angiotensin I levels were identical in both groups. Physical exercise caused an elevation that was more marked in the asthmatic group than in the control group. The activity of serum angiotensin-converting enzyme differed in the two groups even before physical exercise, the asthmatic children having exhibited an activity level significantly lower than that of the healthy controls. after submaximal work, the enzyme activity increased in healthy subjects but decreased in asthmatic children.     

血管紧张素Ⅱ对心房颤动患者外向钾电流的作用

目的：研究血管紧张素Ⅱ(AngⅡ)对心房颤动(AF)患者心房肌外向钾电流的作用及其受体机制。方法: 采用急性酶解法获取游离心房肌细胞，应用膜片钳全细胞技术记录外向钾电流。结果: (1) 在钳制电位-10 mV~+50 mV时, AF组瞬时外向钾电流(I_to1)密度明显低于窦性心律(SR)组（P<0.01），而持续性外向钾电流（I_sus）密度与SR组无明显差异。(2) 以0.1 μmol/L AngⅡ灌流后，在钳制电位0 mV~+50 mV时，SR患者的Ito1密度明显低于灌流前（P<0.01），其动力学特性没有改变，AngⅡ对AF组I_to1的抑制作用明显低于SR组 (P<0.01)。0.1 μmol/L AngⅡ对两组I_sus没有影响。(3) AngⅡ对Ito1的抑制作用可逆，10 μmol/L缬沙坦（valsartan）以及1 μmol/L沙拉新(saralasin)均能完全消除0.1 μmol/L AngⅡ对Ito1的抑制，以10 μmol/L valsartan灌流后，膜电位+50 mV时I_to1的电流密度增加（22.46±4.30）%。结论: AngⅡ通过Ⅰ型受体（AT₁R）介导，明显抑制心房肌细胞膜I_to1，是AF患者心房肌瞬时外向钾通道电重构的机制之一。     

钙激活蛋白酶系统与慢性房颤犬心房重构关系的研究

目的： 探讨慢性房颤犬心房肌钙激活蛋白酶（calpain）系统表达水平的改变及其与心房重构的相关性。方法： 17只杂种犬随机分为心房颤动组（11只）和对照组（6只），于起搏前后均进行经胸超声心动图检查，测量舒张期左房内径。房颤组经颈外静脉将电极置入右心耳快速起搏（400 beats/min）8周复制房颤模型，开胸取心房组织，测定心房肌Ca2+浓度，用荧光实时定量PCR和Western blotting技术检测calpain及其抑制剂calpastatin mRNA和蛋白的表达量。结果： 房颤组心房肌Ca2+浓度升高，左房内径显著大于起搏前及对照组(P<0.05)，房颤组和对照组比较犬心房肌calpainⅠ、calpainⅡmRNA表达无显著差异(P＞0.05)，房颤组calpastatin mRNA表达明显高于对照组(P<0.05)；房颤组calpainⅠ、calpainⅡ蛋白表达明显高于对照组(P<0.05)，calpastatin蛋白表达明显低于对照组(P<0.05)。CalpainⅠ、calpainⅡ蛋白表达水平与左房内径呈显著正相关(r=0.53，r=0.67,P<0.05)，calpastatin蛋白表达水平与左房内径呈显著负相关(r=-0.74，P<0.05)。结论： 房颤所引起calpain系统的蛋白表达改变，使calpain/calpastatin系统相互间作用失衡，造成多种蛋白被降解可能是心房重构的重要机制。     

房颤患者血清对心肌成纤维细胞趋化运动的影响

目的: 研究心肌成纤维细胞的运动特性,以及房颤与非房颤患者血清对成纤维细胞趋化运动诱导能力的差异。方法: 用胰酶和胶原酶消化、差速贴壁法培养新生SD大鼠的心肌成纤维细胞,取3-4代采用Transwell装置检测房颤组血清与非房颤组血清诱导成纤维细胞运动的能力差异。结果: 在各组血清的趋化诱导作用下,与对照组相比,迁移至下室的细胞数明显增多。其中持续性房颤组最多,非房颤房性心律失常组明显高于阵发性房颤组,对照组细胞数最少,各组比较均具有显著差异。Logistic回归分析表明,迁移至滤膜下的细胞数与左房直径以及房颤有相关性。结论: (1)各组血清的趋化诱导能力高于对照组,不同组间的差异说明心房纤维化是一个慢性、隐匿、迁延的过程。以修复为目的的成纤维细胞迁移浸润数量间接反映了心肌损伤的存在、范围和程度。(2)迁移浸润的细胞数变化先于左房直径变化,提示房颤和左房直径增大的正相关关系可能并非直接的因果关系,心房肌损伤后的纤维化可能参与其中。