PREDICTION ROLE OF THE LEFT VENTRICLE REMODELLING IN ARTERIAL HYPERTENSION PATIENTS

Abstract Background Cardiac fibrosis and arterial hypertension are common in patients with chronic kidney disease (CKD). We studied the mechanisms of cardiac fibrogenesis and the role of blood pressure in mice with CKD. Methods and results 10-week-old male C57/BL6N (BL6) and SV129 wildtype (WT) mice were underwent 5/6 nephrectomy (remnant kidney model, RKM) or sham operation for 10 weeks. RKM significantly elevated plasma creatinine and urea. RKM elicited both interstitial and replacement renal and left ventricular (LV) (BL6: SHAM 5.6±0.4%, RKM 7.3±0.7%, p=0.04; SV129: SHAM 6.0±0.5%, RKM 14±2%, p=0.001) fibrosis as assessed by picrosirius red staining. In parallel, the number of cardiac fibroblasts per mm2 (BL6: SHAM 36±4, RKM 85±13, p=0.001; SV129: SHAM 82±11, RKM 200±34, p=0.006) was increased in RKM mice. With regard to possible mechanisms, cardiac oxidative stress as shown by co-immunostaining for intracellular fibronectin and 8-hydroxyguanosine (BL6: SHAM 44±14%, RKM 60±24%, p=0.03; SV129: SHAM 51±6%, RKM 70±7%, p=0.04) and the percentage of CXCR4+ fibroblasts in the myocardium (BL6: SHAM 47±5%, RKM 62±4%, p=0.04; SV129: SHAM 63±5%, RKM 81±3%, p=0.005) were increased. Furthermore, the number of circulating CD45+ / collagen I+ fibrocytes (FACS) in the peripheral blood was increased by RKM in BL6 (SHAM 100±23%, RKM 443±252%, p=0.04) and diminished in SV129 (SHAM 100±19%, RKM 43±11%, p=0.01), while an opposite regulation was seen in the bone marrow. To further confirm the role of bone-marrow derived fibroblasts in renal and cardiac remodeling 10-week-old WT BL6 mice were subjected to transplantation of bone marrow from 10-week-old WT BL6 mice expressing green fluorescent protein (GFP)+ ubiquitously. 28 days later, RKM or SHAM-operation was performed. RKM significantly increased the number of GFP+ fibroblasts in kidney and LV-myocardium. CKD significantly decreased myocardial capillarization assessed by immunostaining for podocalyxin in both mouse lines. In parallel, myocardial protein expression of fibrosis regulators fibronectin, collagen I, CTGF and Hif1a were up-regulated and expression of the active form of eNOS (phospho-S1177) was reduced. As a possible confounder, tail-cuff blood pressure was moderately enhanced (Ø 30mmHg) 9 weeks after nephrectomy. In a control experiment using the vasodilator hydralazine (250 mg/L/day), peripheral blood pressure was equalized in all 4 experimental groups, but the extent of LV fibrosis and expression of the above-mentioned fibrosis markers remained unchanged. Conclusions Chronic kidney disease in the RKM model elicits left ventricle fibrosis by increasing myocardial protein expression of fibrosis regulators, reduction of myocardial capillarization and mobilization / recruitment of circulating fibroblasts, independently of blood pressure. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft

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Insulin-Like Growth Factor-1 and Left Ventricle Remodeling in Patients with Hypertension with Abdominal Obesity

Ukraïnsʹkij žurnal medicini bìologìï ta sportu ◽

10.26693/jmbs06.05.178 ◽

2021 ◽

Vol 6 (5) ◽

pp. 178-183

Author(s):

S. M. Koval ◽

◽

L. A. Reznik ◽

T. G. Starchenko ◽

M. Yu. Penkova

Keyword(s):

Body Weight ◽

Growth Factor ◽

Left Ventricle ◽

Arterial Hypertension ◽

Abdominal Obesity ◽

Left Ventricular ◽

Insulin Like Growth Factor ◽

Normal Body ◽

Normal Body Weight

The purpose of the work is to study the role of insulin-like growth factor-1 in the mechanisms of left ventricular remodeling in patients with arterial hypertension with abdominal obesity and arterial hypertension with normal body weight. Materials and methods. The study included 42 patients with arterial hypertension and abdominal obesity and 22 patients with arterial hypertension and normal body weight. All patients underwent general clinical laboratory and instrumental examination. The structural parameters of the heart were determined using echocardiographic studies. To assess the geometric rearrangement of the left ventricle, the relative thickness of its walls was calculated. Determination of the level of insulin-like growth factor-1 in serum was performed using enzyme-linked immunosorbent assay. Results and discussion. According to echocardiographic studies, left ventricular hypertrophy was diagnosed in 30 patients (71.4%) with arterial hypertension and obesity and in 9 (40.9%) patients with normal body weight (p <0.05). The advantage of hypertrophic types in the structural reconstruction of the heart and the formation of unfavorable types of geometry of the left ventricle in the presence of abdominal obesity in the subjects was found. It was found that in arterial hypertension with abdominal obesity, high levels of insulin-like growth factor-1 were found with normal geometry of the left ventricle, and with concentric hypertrophy and eccentric hypertrophy, a gradual probable decrease in this growth factor was observed and adhered to its comparison with the norm. The attention is drawn not only to the gradual decrease in insulin-like growth factor-1 from normal geometry to concentric and eccentric geometry, but also to the probable differences between this growth factor in concentric geometry and eccentric geometry, indicating the role of insulin-like growth factor-1 deficiency in cardiac remodeling. In normal weight hypertension, probable differences in this growth factor are obtained only between normal and eccentric left ventricular geometry. Сonclusion. Thus, the data obtained may indicate differences in the course of arterial hypertension, aggravated by abdominal obesity, in comparison with patients with hypertension with normal body weight. It is the association of arterial hypertension with abdominal obesity that causes a decrease in the synthesis of insulin-like growth factor-1, as a result of which there is an accelerated development of the pathological geometry of the left ventricle with the subsequent manifestation of heart failure. These results allow us to expand our understanding of the mechanisms of the formation of cardiac damage in patients with arterial hypertension and especially when it is combined with obesity

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The role of diuretics in the treatment of arterial hypertension: focus on new loop diuretic – torasemide

Consilium Medicum ◽

10.26442/2075-1753_2015.10.23-27 ◽

2015 ◽

Vol 17 (10) ◽

pp. 23-27

Author(s):

M.V. Leonova ◽

Keyword(s):

Arterial Hypertension ◽

Loop Diuretic

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Role of genetic factors in the development of hypertension in young patients with metabolic syndrome

Spravočnik vrača obŝej praktiki (Journal of Family Medicine) ◽

10.33920/med-10-2004-03 ◽

2020 ◽

pp. 23-32

Author(s):

Elena Korneeva ◽

Mikhail Voevoda ◽

Sergey Semaev ◽

Vladimir Maksimov

Keyword(s):

Metabolic Syndrome ◽

High Risk ◽

Arterial Hypertension ◽

Genetic Factors ◽

Young Patients ◽

Integrin Αiibβ3 ◽

Ace Gene ◽

The Metabolic Syndrome

Results of the study related to polymorphism of ACE gene (rs1799752)‎, integrin αIIbβ3, and CSK gene (rs1378942) influencing development of arterial hypertension in young patients with metabolic syndrome are presented. Hypertension as a component of the metabolic syndrome was detected in 15.0% of young patients. Prevalence of mutant alleles of the studied genes among the examined patients was quite high, so homozygous DD genotype was found in 21.6%, and mutant D allele of the ACE gene in 47.4%. A high risk of hypertension in patients with MS was detected in carriers of the T allele of the CSK (rs1378942) gene – 54.8%, which was most often observed in a combination of polymorphic ACE and CSK gene loci (p = 0.0053).

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Navigating the Road to Transplant in Pulmonary Arterial Hypertension: A Road Less Taken

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x.15.1.12 ◽

2016 ◽

Vol 15 (1) ◽

pp. 12-13

Author(s):

Adaani E. Frost ◽

Harrison W. Farber

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Lung Transplantation ◽

Small Cell ◽

Small Cell Lung ◽

Donor Organ ◽

The Road ◽

Lung Allocation Score ◽

Pulmonary Arterial

Dramatic advances in therapy for pulmonary arterial hypertension (PAH) in the last 20 years have improved survival from a median of 2.5 years in the pretreatment era to 7.5 years currently. However, impressive as that may seem, it is important to note that a median survival of 7.5 years is equivalent to that of surgically resected non-small cell lung cancer, thus underscoring the importance of lung transplantation as a treatment option in patients with PAH. In this edition of Advances, Edelman has reviewed the pathway to transplantation for patients with PAH, detailing the recommendations for timing of referral, listing for lung transplantation, the role of the lung allocation score in allocating a donor organ, and the outcome of lung transplantation.

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