Major histocompatibility complex and coronary artery disease: Special emphasis on Chlamydia pneumoniae, and periodontitis

Most of the genes in the MHC region are involveed in adaptive and innate immunity, with essential function in inflammatory reactions and in protection against infections. These genes might serve as a candidate region for infection and inflammation associated diseases. CAD is an inflammatory disease. The present set of studies was performed to assess whether the MHC region harbors genetic markers for CAD, and whether these genetic markers explain the CAD risk factors: e.g., C. pneumoniae, periodontitis, and periodontal pathogens. Study I was performed using two separate patient materials and age- and sex-matched healthy controls, categorizing them into two independent studies: the HTx and ACS studies. Both studies consistently showed the HLA-A3– B35– DR1 (35 ancestral haplotype) haplotype as a susceptible MHC genetic marker for CAD. HLA-DR1 alone was associated not only with CAD, but also with CAD risk factor diseases, e.g., diabetes mellitus, and hyperlipidemia. The ACS study further showed the HLA-B*07 and -DRB1*15 -related haplotype as a protective MHC haplotype for CAD. Study II showed that patients with CAD showed signs of chronic C. pneumoniae infection when compared to age- and sex-matched healthy controls. HLA-B*35 or -related haplotypes associated with the C. pneumoniae infection markers. Among these haplotype carriers, males and smokers associated with elevated C. pneumoniae infection markers. Study III showed that CAD patients with periodontitis had elevated serum markers of P. gingivalis and occurrence of the pathogen in saliva. LTA+496C strongly associated with periodontitis, while HLA-DRB1*01 with periodontitis and with the elevated serum antibodies of P. gingivalis. Study IV showed that the increased level of C3/C4 ratio was a new risk factor and was associated with recurrent cardiovascular end-points. The increased C3 and decreased C4 concentrations in serum explained the increased level of the C3/C4 ratio. Both the higher than cut-off value (4.53) and the highest quartile of the C3/C4 ratio were also associated with worst survival, increased end-points, and C4 null alleles. The presence of C4 null alleles associated with decreased serum C4 concentration, and increased C3/C4 ratio. In conclusion, the present studies show that the CAD susceptibility haplotype (HLA-A3− B35− DR1 -related haplotypes, Study I) partially explains the development of CAD in patients possessing several recognized and novel risk factors: diabetes mellitus, increased LDL, smoking, C4B*Q0, C. pneumnoiae, periodontitis, P. gingivalis, and complement C3/C4 ratio (Study II, III, and IV).

Noninvasive techniques in assessing coronary artery disease

Conventional invasive coronary angiography is the clinical gold standard for detecting of coronary artery stenoses. Noninvasive multidetector computed tomography (MDCT) in combination with retrospective ECG gating has recently been shown to permit visualization of the coronary artery lumen and detection of coronary artery stenoses. Single photon emission tomography (SPECT) perfusion imaging has been considered the reference method for evaluation of nonviable myocardium, but magnetic resonance imaging (MRI) can accurately depict structure, function, effusion, and myocardial viability, with an overall capacity unmatched by any other single imaging modality. Magnetocardiography (MCG) provides noninvasively information about myocardial excitation propagation and repolarization without the use of electrodes. This evolving technique may be considered the magnetic equivalent to electrocardiography. The aim of the present series of studies was to evaluate changes in the myocardium assessed with SPECT and MRI caused by coronary artery disease, examine the capability of multidetector computed tomography coronary angiography (MDCT-CA) to detect significant stenoses in the coronary arteries, and MCG to assess remote myocardial infarctions. Our study showed that in severe, progressing coronary artery disease laser treatment does not improve global left ventricular function or myocardial perfusion, but it does preserve systolic wall thickening in fixed defects (scar). It also prevents changes from ischemic myocardial regions to scar. The MCG repolarization variables are informative in remote myocardial infarction, and may perform as well as the conventional QRS criteria in detection of healed myocardial infarction. These STT abnormalities are more pronounced in patients with Q-wave infarction than in patients with non-Q-wave infarctions. MDCT-CA had a sensitivity of 82%, a specificity of 94%, a positive predictive value of 79%, and a negative predictive value of 95% for stenoses over 50% in the main coronary arteries as compared with conventional coronary angiography in patients with known coronary artery disease. Left ventricular wall dysfunction, perfusion defects, and infarctions were detected in 50-78% of sectors assigned to calcifications or stenoses, but also in sectors supplied by normally perfused coronary arteries. Our study showed a low sensitivity (sensitivity 63%) in detecting obstructive coronary artery disease assessed by MDCT in patients with severe aortic stenosis. Massive calcifications complicated correct assessment of the lumen of coronary arteries.

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.

HealthMap: A cluster randomised trial of interactive health plans and self-management support to prevent coronary heart disease in people with HIV

Background The leading causes of morbidity and mortality for people in high-income countries living with HIV are now non-AIDS malignancies, cardiovascular disease and other non-communicable diseases associated with ageing. This protocol describes the trial of HealthMap, a model of care for people with HIV (PWHIV) that includes use of an interactive shared health record and self-management support. The aims of the HealthMap trial are to evaluate engagement of PWHIV and healthcare providers with the model, and its effectiveness for reducing coronary heart disease risk, enhancing self-management, and improving mental health and quality of life of PWHIV. Methods/Design The study is a two-arm cluster randomised trial involving HIV clinical sites in several states in Australia. Doctors will be randomised to the HealthMap model (immediate arm) or to proceed with usual care (deferred arm). People with HIV whose doctors are randomised to the immediate arm receive 1) new opportunities to discuss their health status and goals with their HIV doctor using a HealthMap shared health record; 2) access to their own health record from home; 3) access to health coaching delivered by telephone and online; and 4) access to a peer moderated online group chat programme. Data will be collected from participating PWHIV (n = 710) at baseline, 6 months, and 12 months and from participating doctors (n = 60) at baseline and 12 months. The control arm will be offered the HealthMap intervention at the end of the trial. The primary study outcomes, measured at 12 months, are 1) 10-year risk of non-fatal acute myocardial infarction or coronary heart disease death as estimated by a Framingham Heart Study risk equation; and 2) Positive and Active Engagement in Life Scale from the Health Education Impact Questionnaire (heiQ). Discussion The study will determine the viability and utility of a novel technology-supported model of care for maintaining the health and wellbeing of people with HIV. If shown to be effective, the HealthMap model may provide a generalisable, scalable and sustainable system for supporting the care needs of people with HIV, addressing issues of equity of access. Trial registration Universal Trial Number (UTN) U111111506489; ClinicalTrial.gov Id NCT02178930 submitted 29 June 2014

DECT evaluation of noncalc fied coronary artery plaque

Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (rho(e)) and the effective atomic number (Z(eff)) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purpose of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (rho(e), Z(eff)) lie in the range of (2.65 x 10(23) <= rho(e) <= 3.64 x 10(23)/cm(3)) and (6.80 <= Z(eff) <= 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V-1) and HU(V-2), with V-1,V-2 = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (rho(e), Z(eff)) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (rho(e), Z(eff)) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives Pc with an accuracy of 3.5% while Z(eff) is found within 1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques are practically nonexistent, and microcalcification, as observed in histopathology, has to be taken into account to explain the nature of the observed (rho(e), Z(eff)) data. This also enables us to judge the composition of the plaque in terms of basic model which considers the plaque to be composed of fibres, lipids, and microcalcification. Conclusions: This simple and reliable method has the potential as an effective modality to investigate the composition of noncalcified coronary artery plaques and thus help in their characterization. In this inversion method, (rho(e), Z(eff)) of the scanned sample can be found by eliminating the effects of the CT machine and also by ensuring that the determination of the two unknowns (rho(e), Z(eff)) does not interfere with each other and the nature of the plaque can be identified in terms of a three component model. (C) 2015 American Association of Physicists in Medicine.

Novel nanostructured biomaterials: implications for coronary stent thrombosis.

BACKGROUND: Nanomedicine has the potential to revolutionize medicine and help clinicians to treat cardiovascular disease through the improvement of stents. Advanced nanomaterials and tools for monitoring cell-material interactions will aid in inhibiting stent thrombosis. Although titanium boron nitride (TiBN), titanium diboride, and carbon nanotube (CNT) thin films are emerging materials in the biomaterial field, the effect of their surface properties on platelet adhesion is relatively unexplored. OBJECTIVE AND METHODS: In this study, novel nanomaterials made of amorphous carbon, CNTs, titanium diboride, and TiBN were grown by vacuum deposition techniques to assess their role as potential stent coatings. Platelet response towards the nanostructured surfaces of the samples was analyzed in line with their physicochemical properties. As the stent skeleton is formed mainly of stainless steel, this material was used as reference material. Platelet adhesion studies were carried out by atomic force microscopy and scanning electron microscopy observations. A cell viability study was performed to assess the cytocompatibility of all thin film groups for 24 hours with a standard immortalized cell line. RESULTS: The nanotopographic features of material surface, stoichiometry, and wetting properties were found to be significant factors in dictating platelet behavior and cell viability. The TiBN films with higher nitrogen contents were less thrombogenic compared with the biased carbon films and control. The carbon hybridization in carbon films and hydrophilicity, which were strongly dependent on the deposition process and its parameters, affected the thrombogenicity potential. The hydrophobic CNT materials with high nanoroughness exhibited less hemocompatibility in comparison with the other classes of materials. All the thin film groups exhibited good cytocompatibility, with the surface roughness and surface free energy influencing the viability of cells.

Changes in biomechanical properties of the coronary artery wall contribute to maintained contractile responses to endothelin-1 in atherosclerosis.

AIMS: Our aim was to determine whether alterations in biomechanical properties of human diseased compared to normal coronary artery contribute to changes in artery responsiveness to endothelin-1 in atherosclerosis. MAIN METHODS: Concentration-response curves were constructed to endothelin-1 in normal and diseased coronary artery. The passive mechanical properties of arteries were determined using tensile ring tests from which finite element models of passive mechanical properties of both groups were created. Finite element modelling of artery endothelin-1 responses was then performed. KEY FINDINGS: Maximum responses to endothelin-1 were significantly attenuated in diseased (27±3 mN, n=55) compared to normal (38±2 mN, n=68) artery, although this remained over 70% of control. There was no difference in potency (pD2 control=8.03±0.06; pD2 diseased=7.98±0.06). Finite element modelling of tensile ring tests resulted in hyperelastic shear modulus μ=2004±410 Pa and hardening exponent α=22.8±2.2 for normal wall and μ=2464±1075 Pa and α=38.3±6.7 for plaque tissue and distensibility of diseased vessels was decreased. Finite element modelling of active properties of both groups resulted in higher muscle contractile strain (represented by thermal reactivity) of the atherosclerotic artery model than the normal artery model. The models suggest that a change in muscle response to endothelin-1 occurs in atherosclerotic artery to increase its distensibility towards that seen in normal artery. SIGNIFICANCE: Our data suggest that an adaptation occurs in medial smooth muscle of atherosclerotic coronary artery to maintain distensibility of the vessel wall in the presence of endothelin-1. This may contribute to the vasospastic effect of locally increased endothelin-1 production that is reported in this condition.

Recovery of linear and nonlinear heart rate dynamics after coronary artery bypass grafting surgery

Background: Conventional coronary artery bypass grafting (C-CABG) and off-pump CABG (OPCAB) surgery may produce different patients' outcomes, including the extent of cardiac autonomic (CA) imbalance. the beneficial effects of an exercise-based inpatient programme on heart rate variability (HRV) for C-CABG patients have already been demonstrated by our group. However, there are no studies about the impact of a cardiac rehabilitation (CR) on HRV behaviour after OPCAB. the aim of this study is to compare the influence of both operative techniques on HRV pattern following CR in the postoperative (PO) period.Methods: Cardiac autonomic function was evaluated by HRV indices pre- and post-CR in patients undergoing C-CABG (n = 15) and OPCAB (n = 13). All patients participated in a short-term(approximately 5 days) supervised CR programme of early mobilization, consisting of progressive exercises, from active-assistive movements at PO day 1 to climbing flights of stairs at PO day 5.Results: Both groups demonstrated a reduction in HRV following surgery. the CR programme promoted improvements in HRV indices at discharge for both groups. the OPCAB group presented with higher HRV values at discharge, compared to the C-CABG group, indicating a better recovery of CA function.Conclusion: Our data suggest that patients submitted to OPCAB and an inpatient CR programme present with greater improvement in CA function compared to C-CABG.