Treatment of Coronary Heart Disease from the Perspective of Liver Controlling Dispersion

The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.

Therapies for patients with coexisting heart failure with reduced ejection fraction and non-alcoholic fatty liver disease

Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD.This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD.Pharmacological therapies,including angiotensinconverting enzyme inhibitors/angiotensin receptor blockers,mineralocorticoids receptor antagonist,and sodium-glucose cotransporter-2 inhibitors,have been shown to reduce fibrosis and fat deposits in the liver.However,there are currently no data showing the beneficial effects of sacubitril/valsartan,ivabradine,hydralazine,isosorbide nitrates,digoxin,or beta blockers on NAFLD in patients with HFrEF.This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities.Further research is needed in patients with coexisting HFrEF and NAFLD,with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.

Diagnostic and therapeutic challenge of heart failure after liver transplant:Case series

Heart failure(HF) following liver transplant(LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, echocardiography at rest and on stress, reasonably prognosticates the risk. In patients of chronic liver disease, cirrhotic cardiomyopathy, alcoholic cardiomyopathy, and stress induced cardiomyopathy have each been implicated as a cause for HF after LT. However distinguishing one etiology from another not only is difficult, several etiologies may possibly coexist in a given patient. Diagnostic dilemma is further compounded by the fact that presentation and management of HF irrespective of the possible underlying cause, remains the same. In this case series, 6 cases are presented and in the light of existing literature modification in the preoperative workup are suggested.

Comparative Assessment of Melatonin-Afforded Protection in Liver, Kidney and Heart of Male Mice against Doxorubicin Induced Toxicity

Melatonin (MEL) was investigated for protection against the anthracycline antibiotic doxorubicin (Dox) that is well known for its oxidative damage to various body organs. It was aimed to have a comparison of this protection to heart, liver and kidney in the treated subjects. In this study, groups of mice were treated with Dox and melatonin and their individual or combined effects were evaluated by assessing lipidperoxidation, non-protein sulfhydryls (NP-SH) and nitrate/nitrite (NO) contents in these tissues. Plasma aminotransferases, LDH and CK-MB enzyme activities were measured. Moreover, these tissues were subject to histopathological assessment. MEL co-treatment significantly prevented any rise in lipidperoxides more significantly in heart and liver as compared to kidney. In tandem, MEL prevented a decline in GSH that was observed by Dox alone in liver and kidney. Dox significantly increased total NO levels in all the tissues. Melatonin at both dose levels could not afford protection against nitrosative stress. MEL in combination treatment provided significant

Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.

Sonographic fatty liver, overweight and ischemic heart disease

AIM: To demonstrate the prevalence of sonographic fatty liver, overweight and ischemic heart disease (IHD) among the male workers in Taiwan, and to investigate the possible association of these three factors.METHODS: From July to September 2003, a total of 2 088 male aircraft-maintenance workers aged from 22to 65 years (mean 40.5) underwent an annual health examination, including anthropometrical evaluation, blood pressure measurement, personal medical history assessment,biochemical blood analysis, abdominal ultrasonographic examination and digital electrocardiography (ECG). The Student's t-test, x2 test and multivariate logistic regression analysis were utilized to evaluate the relationship between IHD and salient risk factors.RESULTS: The all-over prevalence of overweight was 41.4%, and that of fatty liver was 29.5% (mild, moderate and severe fatty liver being 14.5%, 11.3%, and 3.7%,respectively); while the prevalence of ischemic changes on ECG was 17.1% in this study. The abnormal rates for conventional IHD risk factors including hypertension,dyslipidemia, hyperglycemia and overweight increased in accordance with the severity of fatty liver. Overweight and severity of fatty liver were independently associated with increased risks for developing IHD. Overweight subjects had a 1.32-fold (95%CI: 1.01-1.73) increased IHD risk. Participants with mild, moderate, and severe fatty liver had a 1.88-fold (95%CI: 1.37-2.6), 2.37-fold (95%CI: 1.66-3.37) and 2.76-fold (95%CI: 1.62-4.72)increased risk for developing IHD. The prevalence of ischemic ECG for the fatty liver-affected subjects with or without overweight was 30.1% and 19.1%, while that of overweight subjects free from fatty liver was 14.4%.Compared to the subjects without fatty liver nor overweight,IHD risk for the three subgroups above was as follows:OR: 2.95 (95%CI:2.31-4.09), OR: 1.60 (95%CI: 1.07-2.39)and OR: 1.11 (95%CI: 0.78-1.56), respectively.CONCLUSION: The presence of fatty liver and its severity should be carefully considered as independent risk factors for IHD. Results of the study suggest the synergistic effect between fatty liver and overweight for developing IHD.Abdominal sonographic examination may provide valuable information for IHD risk assessment in addition to limited report about liver status, especially for overweight males.

Coronary heart disease:Significance of liver X receptor α genomics

Crosstalk between lipid peroxidation and inflammation is known to be a pathognomonic feature for the development of coronary heart disease(CHD).In this regard ligand activated liver X receptor(LXR)-α has emerged as a key molecular switch by its inherent ability to modulate an array of genes involved in these two fundamental cellular processes.In addition,LXR-α has also been found to play a role in hepatic lipogenesis and innate immunity.Although several lines of evidence in experimental model systems have established the atheroprotective nature of LXR-α,human subjects have been reported to possess a paradoxical situation in which increased blood cellular LXR-α gene expression is always accompanied by increased coronary occlusion.This apparent paradox was resolved recently by the finding that CHD patients possess a deregulated LXR-α transcriptome due to impaired ligand-receptor interaction.This blood cellular mutated LXR-α gene ex- pression correlated specifically with the extent of coro- nary occlusion and hence need is felt to devise new synthetic ligands that could restore the function of this mutated LXR-αprotein in order to modulate genes involved in reverse cholesterol transport and suppression of the inflammatory response leading to the effective treatment of CHD.

Emerging pathways of communication between the heart and non-cardiac organs

The breakthrough discovery of cardiac natriuretic peptides provided the first direct demonstration of the connection between the heart and the kidneys for the maintenance of sodium and volume homeostasis in health and disease. Yet,little is still known about how the heart and other organs cross-talk. Here, we review three physiological mechanisms of communication linking the heart to other organs through: i) cardiac natriuretic peptides, ii) the microRNA-208 a/mediator complex subunit-13 axis and iii) the matrix metalloproteinase-2(MMP-2)/C-C motif chemokine ligand-7/cardiac secreted phospholipase A2(sPLA2) axis-a pathway which likely applies to the many cytokines, which are cleaved and regulated by MMP-2. We also suggest experimental strategies to answer still open questions on the latter pathway. In short, we review evidence showing how the cardiac secretome influences the metabolic and inflammatory status of non-cardiac organs as well as the heart.

Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation

Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

Relationship between non-alcoholic fatty liver disease and coronary heart disease

Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease and considered a liver manifestation of metabolic syndrome.It is in close relationship with insulin resistance,obesity,diabetes mellitus,all of which increase risk of cardiovascular disease(CVD).Besides,many studies point out that NAFLD independently contributes to the development of atherosclerosis and CHD.On the other hand,CVDs are the leading cause of death in NAFLD patients.Many pathophysiological changes and molecular mechanisms play an important role in NAFLD for CVD formation.Atherosclerosis is common in NAFLD,which also mainly contributes to the CVD formation and CHD.Many studies linking atherosclerotic CHD and NAFLD are present in the literature.Subclinical CHD,mainly detected by coronary computed tomography views,have been detected more common in NAFLD patients.Presence of NAFLD has been found to be more common in patients with severe CHD and in stable CHD,NAFLD has been found to be associated with more diffuse disease.In acute coronary syndromes,especially in acute myocardial infarction,patients with NAFLD have been found to have poor prognosis when compared with NAFLD free patients.In this review,our aim is to evaluate the relationship between NAFLD and CHD in detail and go over the pathophysiological mechanisms underlying this relationship.

Current status and recent advances of liver transplantation from donation after cardiac death

The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.

Protective effects of L-arginine against ischemia-reperfusion injury in non-heart beating rat liver graft

BACKGROUND: Although the use of non-heart beating donors (NHBDs) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to the high incidence of primary graft loss. Prevention of liver injury in NHBDs will benefit the results of transplantation. This study was conducted to evaluate the protective effects of L-arginine on liver grafts from NHBDs. METHODS: One hundred and four Wistar rats were randomly divided into 7 groups: normal control (n=8) controls 1, 2 and 3 (C-1, C-2, C-3, n=16), and experimental 1, 2 and 3 (E-1, E-2, E-3, n=16). For groups C-1 and E-1, C-2 and E-2, and C-3 and E-3, the warm ischemia time was 0, 30, and 45 minutes, respectively. Liver grafts were flushed with and preserved in 4 degrees C Euro-collins solution containing 1 mmol/L L-arginine for 1 hour in each experimental group. Recipients of each experimental group were injected with L-arginine (10 mg/kg body weight) by tail vein 10 minutes before portal vein reperfusion. Donors and recipients of each experimental control group were treated with normal saline. Then transplantation was performed. At 1, 3, and 24 hours after portal vein reperfusion, blood samples were obtained to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) and plasma endothelin (ET). At 3 hours after portal vein reperfusion, grafts samples were fixed in 2.5% glutaraldehyde for electron microscopic observation. RESULTS: At I hour after portal vein reperfusion, the levels of NO in groups E-1, E-2, E-3 and C-1, C-2, C-3 were lower, while the levels of plasma ET, serum ALT and AST were higher than those in the normal control group (P<0.05). At 1, 3, and 24 hours, the levels of NO in groups E-1, E-2, E-3 were higher, while the levels of plasma ET, serum ALT and AST were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of NO in groups C-2 and C-3 were lower than in group C-1 (P<0.05), and the level of NO in group C-3 was lower than in group C-2 (P<0.05). At 1, 3 and 24 hours, the levels of plasma ET, serum ALT, and AST in groups E-1, E-2, E-3 were lower than those in the corresponding control groups (C-1, C-2, C-3) (P<0.05). The levels of plasma ET, serum ALT, and AST were lower in group C-3 than in groups C-1 and C-2 (P<0.05). Pathological changes in groups E-1, E-2, E-3 were milder than those in the corresponding experimental control groups (C-1, C-2, C-3). CONCLUSIONS: The imbalance between NO and ET plays an important role in the development of ischemia-reperfusion injury of liver grafts from NHBDs. L-arginine can attenuate injury in liver grafts from NHBDs by improving the balance between NO and ET.

The Effect of Atorvastatin on Liver Function among Patients with Coronary Heart Disease in Gaza Strip

Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are considered as one of the most important drugs and the drug of choice for reducing an abnormal cholesterol level. Statins are normally used to decrease the risk of coronary heart disease (CHD), but they tend to be associated with liver adverse effects. The objective of this prospective study was to investigate the effect of atorvastatin therapy on the liver function in patients with CHD. Study comprised of 66 newly diagnosed CHD patients who were selected from UNRWA clinics in the Gaza Strip. The patients were clinically examined and treated with atorvastatin (10 - 40 mg/day). A questionnaire was used to collect the data concerning patient’s characteristics. Total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), liver enzymes tests such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total and direct blood bilirubin were measured before starting treatment and after 3 and 6 months of treatment. The results showed a significant increase in the mean values of ALT, AST, total bilirubin and direct bilirubin levels after 3 months then decreased after the next 3 months, but they were higher than the baseline with insignificant association.

HFRS with Severe Heart Liver and Renal Failure:a Case Report

Hemorrhagic fever with renal syndrome(HFRS) is caused by hantavirus infection,which was characterized by abrupt high fever,systemic hemorrhage,hypotension and renal damage.Although multiple system organ damage was not uncommon,but multiple organ system failure were rare.Hereafter we report one case with simultaneous renal,heart and liver failure.In this case,we received some experience and lessons.

Role of basic studies in expanding the donor pool for liver transplantation

BACKGROUND: Liver transplantation is an effective treatment for end-stage liver disease, but a huge gap remains between the number of people who need a liver transplant and the number of organs available. In order to maximize donor organ access for adult and pediatric recipients, novel surgical and liver replacement procedures have evolved. Newer surgical techniques include split cadaveric liver transplantation and living donor liver transplantation (LDLT). With marginal and abnormal donor livers, despite tremendous advances in surgical technology, individual surgical procedure can not be completely brought into play unless effective measurements and basal studies are undertaken. DATA SOURCES: A literature search of MEDLINE and the Web of Science database using 'liver transplantation' and 'expanding donor pool' was conducted and research articles were reviewed. RESULTS: Therapies directed toward scavenging O(2-), inhibiting nicotinamide adenine dinucleotide phosphate oxidase, and/or immuno-neutralizing tumor necrosis factor-alpha may prove useful in limiting the liver injury induced by surgical procedures such as split liver transplantation or LDLT. Improved donor organ perfusion and preservation methods, modulation of inflammatory cytokines, energy status enhancement, microcirculation amelioration, and antioxidant usage can improve non-heart beating donor liver transplantation. Effective measures have been taken to improve the local conditions of donor cells with steatosis, including usage of fat-derived hormone and inflammatory mediators, ischemic preconditioning, depletion of Kupffer cells, and cytokine antibody and gene therapy. Double-filtration plasmapheresis can effectively reduce HCV viremia and prevent HCV recurrence in patient with high HCV RNA levels after LDLT. CONCLUSIONS: Shortage of grafts and poor function of marginal and abnormal donor grafts put many patients at risk of death in waiting for liver transplantation. Advances in surgical technology, combined with improvement and breakthroughs in basic studies hold a promise in expanding the liver donor pool.

Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease

AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.

Effect of serum γ-glutamyltranferase and albumin levels on the response to cardiac resynchronization therapy in the elderly

Background Several liver function tests have been identified as predictors of hospitalization for heart failure(HF) and death in patients with chronic HF. The relationship between serum γ-glutamyltranferase(GGT) and albumin(SA) levels with the response to cardiac resynchronization therapy(CRT) has not been reliably determined. The aim of the study was to evaluate the impact of liver function tests on the results of CRT in the elderly. Methods Baseline GGT and SA were assessed before CRT device implantation in the elderly(> 70-year-old) patients. The endpoints were:(1) CRT response defined as > 5% left ventricular ejection fraction improvement and no hospitalization for HF or cardiovascular death;(2) hospitalizations;and(3) mortality. Results Eighty of 138(58%) included patients were responders at nine months. Compared to responders, the SA levels were not significantly different(35.1 ± 5.4 vs. 33.6 ± 5.5 g/L, P = 0.103);but the GGT levels, higher(81.6 ± 69.3 vs. 54.7 ± 49.6 U/L, P = 0.013) in non-responders to CRT. GGT level was independently associated with non-response to CRT(P < 0.001, OR = 0.17;95% CI: 0.08–0.38, P < 0.001). GGT cut-off value ≥ 55 U/L was highly predictive of non-response [AUC = 0.65, 64% Sensitivity, 69% Specificity(95% CI: 0.56–0.74)]. GGT ≥ 55 U/L was also associated with higher risk of hospitalization for atrial fibrillation(AF)(95% vs. 83%, P = 0.024). Both SA and GGT had no impact on overall(P = 0.220, P = 0.723) mortality. Conclusions Higher level of GGT is an independent predictor of non-response to CRT in patients over age 70 years and is associated with higher risk of hospitalization for AF. Baseline serum levels of albumin and GGT and have no impact on mortality in elderly patients undergoing CRT.

Organ assessment and repair centers: The future of transplantation is near

Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.

Factors predicting futility of liver transplant in elderly recipients:A single-center experience

BACKGROUND As the population of the United States ages,there has been an increasing number of elderly patients with cirrhosis listed for transplant.Previous studies have shown variable results in terms of the relative survival benefit for elderly liver transplant(LT)recipients.There may be factors that are associated with a poor post-transplant outcome which may help determine which elderly patients should and should not be listed for LT.AIM To identify factors associated with futility of transplant in elderly patients.METHODS This was a retrospective study of all patients above the age of 45 who underwent liver transplantation at our tertiary care center between January 2010 and March 2020(n=1019).“Elderly”was defined as all patients aged 65 years and older.Futile outcome was defined as death within 90 d of transplant.Logistic regression analysis was performed to determine what variables,if any were associated with futile outcome in elderly patients.Secondary outcomes such as one year mortality and discharge to facility(such as skilled nursing facility or long-term acute care hospital)were analyzed in the entire sample,compared across three age groups(45-54,55-64,and 65+years).RESULTS There was a total of 260 elderly patients who received LT in the designated time period.A total of 20 patients met the definition of“futile”outcome.The mean Model of End-Stage Liver Disease scores in the futile and non-futile group were not significantly different(21.78 in the futile group vs 19.66 in the“non-futile”group).Of the variables tested,only congestive heart failure was found to have a statistically significant association with futile outcome in LT recipients over the age of 65(P=0.001).Of these patients,all had diastolic heart failure with normal ejection fraction and at least grade I diastolic dysfunction as measured on echocardiogram.Patients aged 65 years and older were more likely to have the outcomes of death within 1 year of LT[hazard ratio:1.937,confidence interval(CI):1.24-3.02,P=0.003]and discharge to facility(odds ratio:1.94,CI:1.4-2.8,P<0.001)compared to patients in younger age groups.CONCLUSION Diastolic heart failure in the elderly may be a predictor of futility post liver transplant in elderly patients.Elderly LT recipients may have worse outcomes as compared to younger patients.

Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.