Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure.

The angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis plays a significant role in regulating myocardial remodeling and the development of heart failure (HF), with ACE2 being the primary focus. However, contemporary understanding of the membrane-bound form of the human ACE2 protein remains insufficient. The purpose of this study was to determine the expression of ACE2 protein in different cells of the left ventricular myocardium in non-diseased hearts and at various stages of ischemic HF. A total of 103 myocardial tissue samples from the left ventricle underwent quantitative and semi-quantitative immunohistochemical analysis. Upon assessing ACE2 immunostaining in all myocardial cells through unselective digital image analysis, there was no change in the stage A HF group. Nevertheless, the expression of ACE2 membrane protein in cardiomyocytes showed a tendency to increase, while non-cardiomyocyte ACE2 expression decreased significantly (p < 0.001). In the stage B HF group, the intensity of ACE2 immunostaining continued to increase with rising cardiomyocyte ACE2 expression (p < 0.001). Non-cardiomyocyte expression, in contrast, remained similar to that observed in the stage A HF group. In the stages C/D HF group, ACE2 expression reached its highest level in cardiomyocytes (p < 0.001), while ACE2 expression in non-cardiomyocytes was the lowest (p < 0.001). These changes in ACE2 protein levels are associated with left ventricular remodeling in ischemic HF.

Genetical Signature-An Example of a Personalized Skin Aging Investigation with Possible Implementation in Clinical Practice.

We conducted a research study to create the groundwork for personalized solutions within a skin aging segment. This test utilizes genetic and general laboratory data to predict individual susceptibility to weak skin characteristics, leveraging the research on genetic polymorphisms related to skin functional properties. A cross-sectional study was conducted in a collaboration between the Private Clinic Medicina Practica Laboratory (Vilnius, Lithuania) and the Public Institution Lithuanian University of Health Sciences (Kaunas, Lithuania). A total of 370 participants agreed to participate in the project. The median age of the respondents was 40, with a range of 19 to 74 years. After the literature search, we selected 15 polymorphisms of the genes related to skin aging, which were subsequently categorized in terms of different skin functions: SOD2 (rs4880), GPX1 (rs1050450), NQO1 (rs1800566), CAT (rs1001179), TYR (rs1126809), SLC45A2 (rs26722), SLC45A2 (rs16891982), MMP1 (rs1799750), ELN (rs7787362), COL1A1 (rs1800012), AHR (rs2066853), IL6 (rs1800795), IL1Beta (rs1143634), TNF-α (rs1800629), and AQP3 (rs17553719). RT genotyping, blood count, and immunochemistry results were analyzed using statistical methods. The obtained results show significant associations between genotyping models and routine blood screens. These findings demonstrate the personalized medicine approach for the aging segment and further add to the growing literature. Further investigation is warranted to fully understand the complex interplay between genetic factors, environmental influences, and skin aging.

Association between Fibrillin1 Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor ß1 Concentration in Human Plasma.

Transforming growth factor (TGF)-ß1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-ß1 levels are linked to Marfan syndrome (MFS) caused by fibrillin1 (FBN1) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-ß1 levels in human blood plasma and FBN1 rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-ß1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-ß1 by roughly 1 ng/mL. Two copies of FBN1 rs1059177 minor allele (G) were required to have an additive effect on TGF-ß1 levels. We found higher TGF-ß1 concentrations in men compared with women (p = 0.001). A strong correlation between TGF-ß1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-ß1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.

Blood Plasma TGF- ß1 Concentration in Sporadic Dilatative Pathology of Ascending Aorta: More Questions than Answers.

Transforming growth factor ß1 (TGF- ß1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- ß1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- ß1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- ß1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- ß1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1-25.3, and median 6.2 ng/ml, range 1.0-33.1, respectively). There is a significant association between TGF-ß1 concentration and DPAA (OR 1.084, CI 1.027-1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-ß1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-ß1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-ß1 levels with an emphasis on preanalytical phase and the choice of sample.

FBN1 polymorphisms in patients with the dilatative pathology of the ascending thoracic aorta.

OBJECTIVES: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely, rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study for dilatative pathology of the ascending thoracic aorta (DPATA) from Lithuanians. METHODS: We studied 312 patients who had undergone aortic reconstructive surgery for DPATA. These patients were sub-divided according to the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii) post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n = 79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was recruited from a random sample screened within epidemiological studies of the Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase-chain-reaction amplification. RESULTS: Patients within the aortic dissection sub-group had significantly higher minor allele frequencies in all five FBN1 single nucleotide polymorphism (SNPs) studied versus reference group subjects (P < 0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly higher in those with aortic aneurysm when compared with the reference group (P = 0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR 1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes with each phenotype of DPATA was assessed using logistic regression models adjusted for gender, age and hypertension. The additive model best fitted SNPs rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub-group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR 2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95% 2.06-9.01). There were no significant associations between all studied FBN1 SNPs and post-stenotic or bicuspid aortic dilatation. CONCLUSIONS: Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection.

[Changes of heart geometry in patients with ischemic heart disease]. / Serganciuju isemine sirdies liga sirdies geometrijos pokyciai.

OBJECTIVE: The aim of the study was to determine ventricular and atrial cardiometric parameters at preinfarction and postinfarction stage of ischemic heart disease. OBJECT AND METHODS: Cardiometric parameters (mass, endocardial surface area, the tracts of flow and outflow, etc.) of 132 men (mean age of 49.7+/-8.9 years) who had died suddenly during prehospital period (within 6 hours) after the first or repeated acute event of "pure" ischemic heart disease were investigated. These patients had no other, except ischemia, factors predisposing myocardial hypertrophy as well as clinical symptoms of heart failure. The decedents were divided into preinfarction (71 men) and postinfarction ischemic heart disease (61 men) groups. RESULTS: At preinfarction stage of ischemic heart disease, mass and endocardial surface area of all parts of the heart were increased, the tracts of flow and outflow--longer. At postinfarction stage, only corresponding left ventricular and atrial parameters were more increased. CONCLUSIONS: Eccentric type of left ventricular hypertrophy (proportional increase of mass and endocardial surface area) and concentric type of right ventricular and right and left atrial hypertrophy (the part of myocardium mass per unit of endocardial area is greater) were determined at preinfarction stage of ischemic heart disease. At postinfarction stage, at least as far as evidence of heart failure is not overt, only the corresponding left ventricular and atrial hypertrophy progresses.

[Results of morphologic epidemiologic study of coronary arteries in Kaunas population aged 20-69 years: atherosclerotic lesions and their interrelationship]. / 20-69 metu Kauno gyventoju sirdies vainikiniu arteriju morfologinio epidemiologinio tyrimo duomenys: ateroskleroziniai pazeidimai ir ju sasaja.

OBJECTIVE: The object of study was the type, frequency and extent, as well as correlation of atherosclerotic lesions in Kaunas population aged 20-69 years. RESULTS: The frequency and intimal area of raised atherosclerotic lesions (fibrous and complicated plaque and calcinosis) are age-dependent. The increase of raised lesions area seems to alter at different decades of life. In men the most substantial progression in left anterior descending artery was observed at the fourth-fifth, in right coronary artery--at the fifth, and in both arteries of women - at the sixth decade of life. The area of fatty streaks is not dependent on age and comprises approximately 4-5% of intimal surface. We observed weak negative correlation between area of raised lesions and fatty streaks, and strong correlation between the area of all type of raised lesions in all three coronary arteries. CONCLUSIONS: The coronary artery atherosclerosis is progressing with age. Age decades, when increase of raised lesion area is observed, correspond to age periods, in which mortality due to ischemic heart disease increases significantly.