Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly Patients with Coronary Artery Disease with or without Inflammatory Rheumatic Disease

Gerontology ◽  
2017 ◽  
Vol 63 (4) ◽  
pp. 337-349
Author(s):  
Mei Bruton ◽  
Ivana Hollan ◽  
Julie Xiao ◽  
Eva Lindroos ◽  
Knut Mikkelsen ◽  
...  

Background: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes. Objective: To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD. Methods: HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD. Results: Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients. Conclusion: The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events.

2019 ◽  
Vol 27 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Necla Benlier ◽  
Mustafa Bilge Erdoğan ◽  
Serdar Keçioğlu ◽  
Nuri Orhan ◽  
Hülya Çiçek

Background Recently, the role of inflammation in coronary artery disease and the association of inflammatory biomarkers with adverse outcomes have been investigated in many studies. We investigated the relationship between high serum mobility group box 1 protein levels and established risk factors for coronary artery disease. Methods Fifty-five patients who presented to our Cardiovascular Surgery Clinic and subsequently underwent coronary artery bypass surgery for coronary artery disease and 50 healthy subjects presenting to the cardiology outpatient clinic without any cardiovascular problem were included in the study. The mean age was 61.47 ± 9.38 years for patients and 58.20 ± 10.15 years for controls. Results There was no statistically significant difference between groups with respect to age or sex. Family history of coronary artery disease, aspirin use, hypertension, and type 2 diabetes were significantly more prevalent in the patient group versus the control group. A significant difference was found between patients and healthy controls with respect to high mobility group box 1 protein levels ( p = 0.001). Conclusions Serum high mobility group box 1 protein was significantly increased in patients with coronary artery disease in comparison to healthy subjects. No associations were found between high mobility group box 1 protein level and certain risk factors for coronary artery disease.


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e030651
Author(s):  
Sverre Holm ◽  
Ingvild Oma ◽  
Tor-Arne Hagve ◽  
Kjell Saatvedt ◽  
Frank Brosstad ◽  
...  

ObjectivesPatients with various inflammatory rheumatic diseases (IRDs) have increased risk of atherothrombotic disease. Lipoprotein (a) (Lp(a)) is a risk factor for atherosclerosis but its role in IRD with accompanying coronary artery disease (CAD) is still unclear. We aimed to examine if serum Lp(a) levels differed between CAD patients with and without accompanying IRD.DesignA cross-sectional observational, patient-based cohort study.SettingReferred centre for coronary artery bypass grafting in the South Eastern part of Norway.Participants67 CAD patients with IRD (CAD/IRD) and 52 CAD patients without IRD (CAD/non-IRD). All patients were Caucasians, aged >18 years, without any clinically significant infection or malignancy.MethodsLp(a) levels in serum were analysed by particle enhanced immunoturbidimetric assay, and Lp(a) levels were related to clinical and biochemical characteristics of the patient population.ResultsWe found no differences in serum levels of Lp(a) between CAD patients with and without IRD. In general, we found that Lp(a) correlated poorly with clinical and biochemical parameters including C reactive protein with the same pattern in the CAD/non-IRD and CAD/IRD groups.ConclusionsOur data do not support a link between inflammation and Lp(a) levels in CAD and in general Lp(a) levels were not correlated with other risk factors for cardiovascular disease.


2019 ◽  
Vol 1 (9) ◽  
pp. 13-19
Author(s):  
S. V. Topolyanskaya ◽  
T. M. Kolontai ◽  
O. N. Vaculenko ◽  
L. I. Dvoretski

Modern concepts about features of diabetes mellitus in very elderly patients are described in the article. Special attention to the therapeutic methods of management of very elderly patients with diabetes mellitus has been devoted. The results of diabetes mellitus study in patients with coronary artery disease older than 75 years in comparison with younger patients are presented.


2020 ◽  
Vol 16 ◽  
Author(s):  
George Kassimis ◽  
Grigoris V. Karamasis ◽  
Athanasios Katsikis ◽  
Joanna Abramik ◽  
Nestoras Kontogiannis ◽  
...  

Coronary artery disease (CAD) remains the leading cause of cardiovascular death in octogenarians. This group of patients represents nearly a fifth of all patients treated with percutaneous coronary intervention (PCI) in real-world practice. Octogenarians have multiple risk factors for CAD and often greater myocardial ischemia than younger counterparts, with a potential of an increased benefit from myocardial revascularization. Despite this, octogenarians are routinely under-treated and belittled in clinical trials. Age does make a difference to PCI outcomes in older people, but it is never the sole arbiter of any clinical decision, whether in relation to the heart or any other aspect of health. The decision when to perform revascularization in elderly patients and especially in octogenarians is complex and should consider the patient on an individual basis, with clarification of the goals of the therapy and the relative risks and benefits of performing the procedure. In ST-segment elevation myocardial infarction (MI), there is no upper age limit regarding urgent reperfusion and primary PCI must be the standard of care. In non-ST-segment elevation acute coronary syndromes, a strict conservative strategy must be avoided; whereas the use of a routine invasive strategy may reduce the occurrence of MI and need for revascularization at follow-up, with no established benefit in terms of mortality. In stable CAD patients, invasive therapy on top of the optimal medical therapy seems better in symptom relief and quality of life. This review summarizes the available data on percutaneous revascularization in the elderly patients and particularly in octogenarians, including practical considerations on PCI risk secondary to ageing physiology. We also analyse technical difficulties met when considering PCI in this cohort and the ongoing need for further studies to ameliorate risk stratification and eventually outcomes in these challenging patients.


MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Chandan k Jha ◽  
Jamsheed Javid ◽  
Suriya Rehman ◽  
...  

Aim: Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of the coronary artery diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases. Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using amplification refractory mutation system PCR method (ARMS-PCR). Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95 % CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95 % CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95 % CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with an increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.


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