Cardiovascular and psychosocial risks among patients below age 50 with acute myocardial infarction

BackgroundDespite improvements in the treatment and prevention of cardiovascular disease since the 1960s, the incidence of cardiovascular diseases among young people has remained the same for many years. This study aimed to compare the clinical and psychosocial attributes of young persons affected by myocardial infarction under the age of 50 years compared to middle-aged myocardial infarction patients 51-65 years old.MethodsData from patients with a documented STEMI or NSTEMI elevated acute myocardial infarction in the age groups up to 65 years, were collected from cardiology clinics at three hospitals in southeast Sweden. The Stressheart study comprised a total of 213 acute myocardial infarction patients, of which n = 33 (15.5%) were under 50 years of age and n = 180 (84.5%) were middle-aged, (51-65 years). These acute myocardial infarction patients filled in a questionnaire at discharge from the hospital and further information through documentation of data in their medical records.ResultsBlood pressure was significantly higher in young compared to middle-aged patients. For diastolic blood pressure (p = 0.003), systolic blood pressure (p = 0.028), and mean arterial pressure (p = 0.005). Young AMI patients had a higher (p = 0.030) body mass index (BMI) than the middle-aged. Young AMI patients were reported to be more stressed (p = 0.042), had more frequently experienced a serious life event the previous year (p = 0.029), and felt less energetic (p = 0.044) than middle-aged AMI patients.ConclusionsThis study revealed that persons under the age of 50 affected by acute myocardial infarction exhibit traditional cardiovascular risk factors like high blood pressure, and higher BMI, and were more exposed to some psychosocial risk factors. The risk profile of young persons under age 50 affected by AMI was in these respects more exaugurated than for middle-aged persons with AMI. This study underlines the importance of the early discovery of those at increased risk and encourages preventative actions to focus on both clinical and psychosocial risk factors.Funding Agencies|Linkoeping University; Swedish AFA Insurance, Stockholm [160340]</p

Suppressed immune profile in children with type 1 diabetes in combination with celiac disease

Introduction: Cytokines, chemokines, acute phase proteins (APP), adipocytokines and matrix metalloproteinases (MMP) are involved in different pathophysiological processes of inflammatory character. The role of the different immune markers and the peripheral immunoregulatory milieu in children diagnosed with type 1 diabetes (T1D) in combination with celiac disease (CD) is not fully understood and is not well studied. The purpose of the present study was therefore to acquire more knowledge and to gain deeper understanding on peripheral immunoregulatory milieu in children with T1D and/or CD. Methods: The study included children diagnosed with T1D in combination with CD (n=18), children with T1D (n=27) or CD (n=16), and reference children (n=42). Blood samples were collected, and serum stored in -80°C until analysis, avoiding multiple freeze-thaw cycles. The inflammatory cyto/chemokines (IL-1β, -5, -6, -8, -9, -10, -13, -15, -17A, -22, -25, -33, IFN-γ, TNF-α, G-CSF, MCP-1, MIP-1α, MIP-1β), diabetes related immune markers (visfatin, resistin), APP (procalcitonin (PTC), ferritin, tissue protein activator, fibrinogen, serum amyloid A) and matrix metalloproteinases (MMP-1, -2, -3) were analyzed with Luminex technique using Bio-Plex assays. Hierarchical cluster analysis was used to identify similarities/differences in immune profiles between children with double diagnosis and children with single diagnosis and reference children. Mann-Whitney U test was used for comparison of the different diagnosis groups within the clusters and whole cohort, respectively. Results: The largest cluster included 75% of the participants and the diagnose distribution in the cluster were very similar to the distribution in the whole study cohort. The remaining 25% were divided in two smaller clusters representing 15.5% and 6.5% respectively. The major finding of this study showed that children with double diagnosis had (1) lower serum levels of IL-22, MCP-1, PCT, visfatin and MMP-2 compared to children with T1D; and (2) lower serum levels of the APC associated chemokine MIP-1α compared to reference children, observed in the main cluster. Most of these observations were also seen in the whole cohort.   Conclusion: Our observations indicate decreased serum levels of IL-22, MIP-1α, MCP-1, PCT, visfatin and MMP-2 in children diagnosed with T1D in combination with CD. These results indicate a suppressed immune profile including Th17 cytokines, chemokines, acute phase proteins, diabetes-related and matrix metalloproteinase immune markers. Functional studies of the involved immune cells (CD4+ Treg, CD8+ Treg, NK-cells and dendritic cells) could contribute to elucidate the heterogeneous immunological processes in children with more than one autoimmune disease

Elevated levels of cortisol in hair precede acute myocardial infarction

Long term stress exposure is typical for modern societies and might trigger different diseases. This case-control study reveals that persons who had suffered an acute myocardial infarction (AMI) had elevated cortisol concentrations in the month before the acute event. Middle-aged patients admitted to cardiology clinics with acute myocardial infarction (AMI) (n=174) were compared to 3156 controls from a population-based cohort in southeast Sweden. The median Hair Cortisol Concentrations (HCC) for those who had suffered an AMI was 53.2 pg/mg compared to 22.2 pg/mg for the control group (p&amp;lt;0.001). In bivariate analysis, higher levels of HCC were strongly (OR=5.69) and statistically significantly associated with current AMI status. The discrimination of cases with AMI from controls remained statistically significant (OR=5.04) even after controlling for established cardiovascular risk factors in a multivariate analysis. Middle-aged persons with acute myocardial infarction had significantly elevated cortisol levels during the month before the cardiac event. This was evident for both men and women. The biomarker cortisol concentration was independently and statistically significantly related to AMI. Chronic stress seems to be a new promising risk factor for AMI.Funding Agencies|Linkoping University Library</p

Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation. CC BY 4.0© 2021 Maria Araceli Diaz Cruz et al., published by De Gruyter 2021.Corresponding author: Maria Araceli Diaz Cruz, Research School of Health and Welfare, School of Health and Welfare, Jönköping University, Jönköping, Sweden, e-mail: [email protected], tel: +46-737553177This study was financially supported by Högskolans Jubileumsfond at the University College of Skövde (Dnr HS 2015/536). Jönköping University provided with open access funding and the necessary resources to carry out this investigation.</p

Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer

Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression. CC BY 4.0</p