The evaluation of expression of receptor and regulatory proteins genes in the myocardium of rats with chronic heart failure

Author(s):  
Л.М. Кожевникова ◽  
И.Б. Цорин ◽  
В.Н. Столярук ◽  
М.Б. Вититнова ◽  
В.В. Барчуков ◽  
...  

Цель исследования - оценка уровня экспрессии генов рецепторных и регуляторных белков, участвующих в процессах ремоделирования и сократимости миокарда у крыс с хронической сердечной недостаточностью. Методика. Использован комплекс эхокардиографических и молекулярно-биологических методов исследования. Экспрессию генов оценивали по уровню мРНК в образцах тканей левого желудочка крыс на 92 сут. после перевязки коронарной артерии (опытная группа) или подведения лигатуры под коронарную артерию (группа сравнения). Выделение РНК из тканей левого желудочка сердца проводили с помощью набора GeneJET, синтез кДНК - используя набор RevertAid H Minus First Strand cDNA Synthesis Kit («Thermo Fisher Scientific», США), ПЦР-РВ проводили с помощью набора qPCRmix-HS («Евроген», Россия), используя праймеры и флуоресцентные зонды («ДНК-синтез», Россия), согласно протоколам производителей. Результаты. Установлено, что хроническая сердечная недостаточность (ХСН) формируется через 90 сут. после воспроизведения переднего трансмурального инфаркта миокарда, о чем свидетельствовало снижение инотропной функции сердца и увеличение конечно-систолического и конечно-диастолического размеров левого желудочка сердца. Показано, что при ХСН повышается экспрессия генов, причастных к ремоделированию миокарда. Так, в биоптатах левого желудочка сердца крыс с ХСН на 41% (p = 0,006) возрастает уровень мРНК для ангиотензиновых рецепторов AT1А-типа, на 33% (р = 0,01) для вазопрессиновых V1A-R и на 71% (p = 0,01) для эндотелиновых ETA-R по сравнению с аналогичными показателями у ложнооперированных животных. У крыс с ХСН уровень мРНК b-AR и b-AR в левом желудочке превышал таковой у ложнооперированных животных соответственно на 35% (p = 0,001) и 48% (p = 0,0001). Выявлен высокий уровень экспрессии генов белков Epac2 и СаМ, играющих ключевую роль в аритмогенезе, что свидетельствует о высокой степени риска развития аритмий при ХСН. Установлено, что у животных с ХСН уровень мРНК для Sigma-R в биоптатах тканей миокарда левого желудочка возрастает на 74% (p = 0,0001) по сравнению с уровнем мРНК в сердцах ложнооперированных крыс, что, по-видимому, носит компенсаторный характер, направленный на поддержание протеостаза, модуляцию активности различных ионных каналов и нормализацию биоэнергетических процессов в миокарде. Заключение. Таким образом, при ХСН в левом желудочке сердца крыс повышается экспрессия генов рецепторных и регуляторных белков, участвующих в процессах ремоделирования миокарда, что может быть одним из механизмов нарушения сократимости миокарда и возникновения злокачественных нарушений сердечного ритма, которые отягощают течение данного заболевания. The purpose. The purpose of the study is to assess the level of expression of receptor and regulatory proteins genes involved in remodeling and myocardial contractility in rats with chronic heart failure. Methods. A complex of echocardiographic and molecular biological research methods was used. Gene expression was assessed by the level of mRNA in tissue samples of the left ventricle of rats extracted on day 92 after the coronary artery ligation (CHF group) or summation of the ligature under the coronary artery (sham-operated group). RNA isolation from the left ventricular tissue of the heart was performed using the GeneJET kit, cDNA synthesis using the RevertAidTM H Minus First Strand cDNA Synthesis Kit (Thermo Fisher Scientific, USA), PCR-RV was performed using the qPCRmix-HS kit (Evrogen, Russia), using primers and fluorescent probes (DNA synthesis, Russia), according to manufacturers protocols. Results. It has been established that chronic heart failure (CHF) is formed 90 days after the reproduction of anterior transmural myocardial infarction, as evidenced by a decrease in heart pumping function and an increase in the end-systolic and end-diastolic sizes of the heart left ventricle. It is shown that CHF increases the expression of genes involved in myocardial remodeling. Thus, in left ventricular biopsy samples of rats with CHF, the level of mRNA for angiotensin receptors of AT1A type increases by 41% (p = 0.006), by 33% (p = 0.01) for vasopressin V1A-R and by 71% (p = 0.01) for endothelin ETA-R compared with similar indicators in sham-operated animals. In rats with CHF, the b1-AR and b2-AR mRNA levels in the left ventricle exceeded that in the sham-operated animals, respectively, by 35% (p = 0.001) and 48% (p = 0.0001). A high level of gene expression of the Epac2 and CaM proteins, which play a key role in arrhythmogenesis, is evidenced, which indicates a high risk of developing arrhythmias in CHF. In animals with CHF, the level of mRNA for Sigma-R in biopsy specimens of left ventricular myocardial tissue was found to increase by 74% (p = 0.0001) compared to the level of mRNA in the hearts of sham-operated rats, that apparently has compensatory character at maintaining proteostasis, modulating the activity of various ion channels and normalizing bioenergetic processes in the myocardium. Conclusion. Thus, with CHF in the left ventricle of the rat heart, gene expression of receptor and regulatory proteins involved in myocardial remodeling increases, which can be one of the mechanisms of violation of myocardial contractility and the occurrence of malignant heart rhythm disorders that make it difficult for the disease.

2015 ◽  
Vol 17 (2) ◽  
pp. 160 ◽  
Author(s):  
Fujian Duan ◽  
Zhi Qi ◽  
Sheng Liu ◽  
Xiuzhang Lu ◽  
Hao Wang ◽  
...  

Aims: The graft of stem cells to treat ischemic cardiomyopathy is popular in many clinical trials. The aim of this study was to evaluate the effectiveness of isolated coronary artery bypass graft combined with bone marrow mononuclear cells (BMMNC) delivered through graft vessels to improve left ventricular remodeling of patients with previous myocardial infarc- tion and chronic heart failure using echocardiography. Material and methods: Patients with previous myocardial infarction and chronic heart failure were randomly allocated to one of the two groups: CABG only (18 patients), or CABG with BMMNC transplantation (24 patients). Echocardiographic parameters were measured on B-mode imaging, 3D imaging and color flow imaging. Results Post-operative LVEDD (end-diastolic dimension of left ventricle), LVESD (end-systolic dimension of left ventricle), LVEDV (end-diastolic volume of left ventricle), LVESV (end-systolic volume of left ventricle), LVEDVI (LVEDV indexed to body surface area), LVESVI (LVESV indexed to body surface area), LV-mass (mass of left ventricle) and LV- massI (LV-mass indexed to body surface area) were significantly improved compared with those obtained prior to operation in CABG+BMMNC group (al p0.05). Postoperative mitral regurgitation score was not significantly different from those prior to opera- tion in both groups (al p>0.05). In Chi-square tests, LVEDD, LVESD, LVEDV, LVESV, LVEDVI, LVESVI, LV-mass, LV- massI were determinants of the left ventricular remodeling. Conclusion: The improvement of left ventricular remodeling in CABG+BMMNC group was better than in the CABG group and this improvement was verified by echocardiography.


2021 ◽  
Vol 23 (1) ◽  
pp. 17-23
Author(s):  
V. A. Lysenko

Chronic heart failure (CHF) does not lose its leading position among the problems of cardiovascular disease. Pathological cardiac remodeling combines the processes of hypertrophy and dilatation of cavities and is the main cause of heart failure progression, and consequently results in high cardiac mortality, especially in CHF patients with reduced left ventricular ejection fraction (LV EF). Despite a substantial range of studies on the features of structural and geometric remodeling of the heart, changes in systolic and diastolic function of the ventricles in CHF patients, this issue still presents a challenge and needs to be improved. The aim of the work – to examine changes in structural and geometric parameters and diastolic function of the heart in patients with CHF of ischemic genesis with reduced LV EF. Materials and methods. The study included 79 patients (men – n = 49; women – n = 30) with CHF of ischemic origin with reduced LV EF, sinus rhythm, stage II AB, NYHA II-IV FC (the main group), and 90 patients with coronary heart disease without signs of CHF (men – n = 40, 44.5 %; women – n = 50, 55.5 %), (the comparison group). The patient groups were age-, sex-, height-, weight-, body surface area-matched. Doppler echocardiographic examination was performed on the device Esaote MyLab Eight (Italy). Results. In CHF patients with reduced LV EF, the following indicators prevailed: EDD LV by 18 % (P = 0.001), LV EDV by 45.8 % (P = 0.001), LV EDV index by 44.6 % (P = 0.001), LV ESD by 44.9 % (P = 0.001), PW by 17.7 % (P = 0.001), LV mass index by 66.6 % (P = 0.001) according to the Penn Convention, and by 62.1 % (P = 0.001) according to the ASE; 16.1 % (P = 0.010) increased RV cavity without changes in its wall thickness. In patients with CHF of ischemic origin with reduced LV EF, the main types of LV geometry were: eccentric (70 %) and concentric (24 %) LV hypertrophy. More than half of the CHF patients with reduced LV EF had significant disorders of LV diastolic filling (25 % – “restrictive” and 28 % “pseudonormal”), a 2.3 times increase (P = 0.001) in E/e’ ratio, a 35 % (P = 0.014) increase in the left atrial volume index and 32 % (P = 0.0001) – in pulmonary capillary wedge pressure (PCWP), increased mean and systolic pressure in the pulmonary artery by 1.5 times (P = 0.002) and 1.6 times (P = 0.0001), respectively. Conclusions. Structural and geometric remodeling of the left ventricle in patients with CHF of ischemic origin with reduced LV EF occurs due to an increase in LV myocardial mass via thickening of its walls and cavity dilatation (44.6 % (P = 0.001) increase in the LV EDV index), as well as 66.6 % (P = 0.001) increase in LV mass index with the predominance of eccentric (70 %) and concentric hypertrophy (24 %) over other types of LV geometry. Severe disorders of LV diastolic filling (25 % – “restrictive” and 28 % “pseudonormal”) are attributable to the significant increase in end-diastolic pressure in the left ventricle (2.3 times increase (P = 0.001) in E/e´) with the development of postcapillary pulmonary hypertension (1.5 times increase (P = 0.002) in the mean and 1.6 times (P = 0.0001) – in systolic pressure in the pulmonary artery).


2016 ◽  
Vol 22 (1) ◽  
pp. 31-36
Author(s):  
Ol’ga N. Dzhioeva ◽  
E. V Kartashova ◽  
I. I Zakharova ◽  
A. V Melekhov ◽  
G. E Gendlin

The left ventricular non-compaction is a disease characterizing by hyper-trabecularization of myocardium causing development of chronic heart failure. In the development of structural damages under this pathology the main role belongs to genetic disorders and dysfunction of organogenesis in early periods of gestation. The clinical manifestations are associated with development of systolic dysfunction of left ventricle, intricate abnormalities of rhythm and thromboembolic occurrences. In patients with systolic dysfunction of left ventricle phenomenon of hyper-trabecularization of myocardium is quite often found during transthoracic echocardiography. The modern diagnostic criteria permit approaching differentially issues of verification of non-compact myocardium and redundant trabecularization in patients with chronic heart failure with reduced fraction of output of left ventricle.


2020 ◽  
pp. 4-13
Author(s):  
А.А. Сафиуллина ◽  
Т.М. Ускач ◽  
М.А. Саидова ◽  
С.В. Добровольская ◽  
С.Н. Терещенко

Обзор посвящен роли современной трансторакальной эхокардиографии и новому способу неинвазивной оценки сократительной функции левого желудочка – исследованию эффективности миокардиальной работы у пациентов хронической сердечной недостаточностью. Освещаются актуальные аспекты ремоделирования левого желудочка и левого предсердия у данной категории пациентов. Обсуждается роль и важность метода спекл-трекинг эхокардиографии в оценке механической функции левого предсердия. Представлены сведения об относительно новом электрофизиологическом методе лечения - модуляции сердечной сократимости у пациентов с хронической сердечной недостаточностью, как с фибрилляцией предсердий, так и без нее. Анализируются результаты обратного ремоделирования левого желудочка по данным эхокардиографических параметров основных исследований, посвященных модуляции сердечной сократимости. В статье оцениваются перспективы применения метода оценки эффективности миокардиальной работы левого желудочка как инструмента возможного обратного ремоделирования у пациентов с хронической сердечной недостаточностью и фибрилляцией предсердий на фоне модуляции сердечной сократимости The review is devoted to the role of modern transthoracic echocardiography and a new method of non-invasive assessment of left ventricular contractile function-the study of the effectiveness of myocardial work in patients with chronic heart failure. The current aspects of left ventricle and left atrium remodeling in this category of patients are highlighted. The role and importance of speckle-tracking echocardiography in evaluating the mechanical function of the left atrium is discussed. Information is provided about a relatively new electrophysiological method of treatment-modulation of heart contractility in patients with chronic heart failure, both with and without atrial fibrillation. The results of reverse remodeling of the left ventricle are analyzed according to the echocardiographic parameters of the main studies devoted to the modulation of heart contractility. The article assesses the prospects for using the method of evaluating the effectiveness of left ventricular myocardial function as a tool for possible reverse remodeling in patients with chronic heart failure and atrial fibrillation against the background of heart contractility modulation


2016 ◽  
Vol 311 (2) ◽  
pp. H337-H346 ◽  
Author(s):  
Hong Zheng ◽  
Xuefei Liu ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/d t to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/d t (by 71%) and −dP/d t (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.


2014 ◽  
Vol 95 (3) ◽  
pp. 362-366
Author(s):  
G M Dadashova

Aim. To determine the gender differences in risk factors of left ventricular remodeling in patients with chronic heart failure associated with arterial hypertension and coronary heart disease. Methods. The study included 112 patients aged 45 to 60 years with myocardial scaring after myocardial infarction and functional class I-III of heart failure by NYHA. Patients were distributed to 2 groups: 1st included 60 males (mean age 54.8±3.3 years), 2nd - 52 females (mean age 55.8±3.1 years). To assess the cardiac function, all patients underwent echocardiography (B- and M-modes). Models of left ventricle architectonics were identified according to such parameters as left ventricle wall relative thickness index and left ventricular mass index. Results. Leading causes for heart failure in female patients were hypertension (50% of cases) and ischemic heart disease (23.1% of cases, 79.5% of ischemic heart disease cases were not associated). In males, ischemic heart disease was the leading reason for chronic heart failure (78.3% of cases, among them 80.9% with a history of survived myocardial infarction). In females, chronic heart failure was more often associated with isolated diastolic dysfunction (78.8% of cases versus 65% in males, p 0.05), and left ventricle ejection fraction was stable. Unfavorable types of left ventricle remodeling in terms of prognosis were more common among females, including eccentric left ventricle hypertrophy (67.3% of cases versus 53.3% in males, p 0.05) and concentric left ventricle hypertrophy (21% of cases versus 18.3% in males, p 0.05). Conclusion. There are gender differences in patients with chronic heart failure: prevalence of hypertension in women, and coronary heart disease in men; higher rate of isolated diastolic dysfunction prognostically unfavorable types of left ventricle remodeling (eccentric and concentric left ventricle hypertrophy) in females.


2014 ◽  
Vol 2 (1) ◽  
pp. 20-24
Author(s):  
M. Klunnyk ◽  
N. Sych ◽  
I. Matiyaschuk ◽  
O. Ivankova ◽  
M. Demchuk ◽  
...  

Fetal stem cells treatment (FSCT) is assumed to be a new direction in a combined therapy for the patients with the severe chronic heart failure (CHF).Material and methods. 20 patients (average age of 50.1 ± 1.1 yrs.) with CHF functional class III-IV (FC) undergoing the transplantation of the cryopreserved cells of the fetal liver and heart obtained from 5-8 weeks gestation embryos were examined. The control group (CG) of 20 patients was compared by gender and age with the main group (MG).Results. Within 6 months after FSC therapy CHF patients reported a significant improvement of the contractile activity of the left ventricle (LV) heart muscle in echocardiography (EchoCG) findings (left ventricular ejection fraction (LVEF) increased by 20.9 % being 2-fold higher than in patients without FSCT, p<0.05) and in features of LV remodeling (left ventricle end diastolic volume (LV EDV) decreased by 20.5 %, p < 0.05). Serum NT-proBNP significantly raised within 1 month after FSCT by 33.8 %, 50 % and 65.1 % in 1, 3 and 6 months respectively (p<0.001) and was significantly lower after a month of treatment compared with CG (р<0.05).As a result of general condition improvement in CHF patients significant elevation in 6 minute walking distance (6MWD) test was observed and the distance walked increased 7.3-fold (p<0.001), 10.3-fold (p<0.001) and 12.5-fold (p<0.001) vs. the baseline in 1, 3 and 6 months, respectively, which was generally 2-fold higher than in patients of the CG. DASI score increased by 54.6 %, after 3 months — by 63.2 %, after 6 months — by 66.4 %, which is significantly higher than the baseline (p<0.05 vs. baseline).Conclusion. It has been proven that combined treatment of CHF patients using FSCs along with the standard therapy increases the LV myocardial contractility, lowering the blood serum NT-proBNP level and results in overall life quality improvement among the patients.


2017 ◽  
Vol 126 (08) ◽  
pp. 478-486
Author(s):  
Pingan Chen ◽  
Lina Hou ◽  
Yishan Luo ◽  
Lushan Chen ◽  
Shaonan Li ◽  
...  

Abstract Background Serum 2-oxoglutarate can reflect the severity of chronic heart failure (CHF) in patients without diabetes. Whether this predictive role persists in type 2 diabetes mellitus (T2DM) patients is unclear. In this study, we investigated this predictive role in T2DM patients and whether 2-oxoglutarate can indicate the diastolic or systolic function of left ventricle. Methods One hundred eighty CHF patients (76 with T2DM) and 66 healthy controls were studied. 2-Oxoglutarate was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Echocardiographic parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured. Results 2-Oxoglutarate was increased in CHF patients with or without T2DM compared with controls (both P<0.01). Patients with a lower left ventricular ejection fraction or a higher NT-proBNP or left ventricular end-diastolic volume index had higher levels of 2-oxoglutarate (median, 18.77 μg/mL versus 11.25 μg/mL; median, 14.06 µg/ml versus 9.39 µg/ml; median, 18.06 µg/mL versus 11.60 µg/mL, all P<0.05) in nondiabetic patients but not in T2DM patients. In multiple logistic regression analysis, NT-proBNP (OR=3.445, 95% CI=1.098 to 10.816, P=0.034) and left ventricular end-diastolic diameter (OR=2.544, 95% CI=1.033 to 6.268, P=0.042) were independently associated with increased 2-oxoglutarate in nondiabetic patients. Conclusions The levels of 2-oxoglutarate can reflect the clinical severity of CHF in nondiabetic patients but not in those with T2DM, and it can be used as a potential indicator of the systolic dysfunction of the left ventricle.


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