Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved left ventricle (LV) function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.NEW & NOTEWORTHY Glutamine metabolism is altered in both infarct macrophages and the remote left ventricle (LV) following myocardial infarction (MI). Supplemental glutamine improves LV function following MI while inhibiting glutamine metabolism with BPTES worsens LV function. Supplemental glutamine or BPTES does not impact macrophage immunometabolic phenotypes after MI.

Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Efficacy and muscle safety assessment of fukutin-related protein gene therapy.

Limb-girdle muscular dystrophy type R9 (LGMDR9) is a muscle-wasting disease that begins in the hip and shoulder regions of the body. This disease is caused by mutations in fukutin-related protein (FKRP), a glycosyltransferase critical for maintaining muscle cell integrity. Here we investigated potential gene therapies for LGMDR9 containing an FKRP expression construct with untranslated region (UTR) modifications. Initial studies treated an aged dystrophic mouse model (FKRPP448L) with adeno-associated virus vector serotype 6 (AAV6). Grip strength improved in a dose- and time-dependent manner, injected mice exhibited fewer central nuclei and serum creatine kinase levels were 3- and 5-fold lower compared to those in non-injected FKRPP448L mice. Treatment also partially stabilized the respiratory pattern during exercise and improved treadmill running, partially protecting muscle from exercise-induced damage. Western blotting of C2C12 myotubes using a novel rabbit antibody confirmed heightened translation with the UTR modifications. We further explored the question of FKRP toxicity in wild-type mice using high doses of two additional muscle-tropic capsids: AAV9 and AAVMYO1. No toxic effects were detected with either therapeutic agent. These data further support the feasibility of gene therapy to treat LGMDR9.

Decreasing tobacco use promotes ulcer healing in a patient with Buerger's disease.

Tobacco cessation remains the mainstay treatment for Buerger's Disease; however, limited research exists examining the effect of decreased tobacco use rather than cessation in improving symptoms. We describe a case of a patient with Buerger's disease who experienced ulcer healing and pain improvement through reduced tobacco use.

Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Mortality Rates and autopsy findings in fat embolism syndrome complicating sickle cell disease.

Fat embolism syndrome is a rare but underdiagnosed complication of sickle cell disease associated with high morbidity and mortality. It affects predominantly patients with a previously mild course of their illness and those of non-SS genotypes while there is possibly an association with infection with human parvovirus B19 (HPV B19). Here, we present the mortality rates and autopsy findings of all reported cases to date. A systematic review has revealed 99 published cases in the world literature with a mortality rate of 46%. Mortality varied greatly according to the time of reported cases with no survivors in the 1940s, 1950s or 1960s and no deaths since 2020. 35% of cases had previously undiagnosed sickle cell disease and the latter was only identified at autopsy after developing fat embolism with a fatal outcome. 20% of cases reported after 1986 tested positive for HPV B19 with an associated mortality of 63% whereas in cases that have not documented HPV B19 infection the mortality was 32%. The organs most often staining positive for fat were the kidneys, lungs, brain and heart whereas ectopic haematopoietic tissue was found in 45% of the examined lung specimens.

Smartphone Application for Smoking Cessation (Quit with US): A Randomized Controlled Trial among Young Adult Light Smokers in Thailand.

This study aimed to determine the efficacy of a smartphone application named Quit with US among young adult smokers. An open-label, parallel, 2-group, randomized controlled trial with a 12-week follow-up was conducted between March and November 2020 among undergraduate students (18 to 24 years) in Chiang Mai Province, Thailand. A total of 273 participants were assigned by simple randomization procedure to the Quit with US intervention group (n = 137) or the control group (n = 136). All participants received pharmacists' smoking cessation counseling at baseline and follow-ups. In addition, the intervention group's participants were advised to use Quit with US. The baseline and 12-week follow-up assessments were conducted at a study unit, whereas other follow-ups were completed over the telephone. The primary abstinence outcome was the exhaled CO concentration level (≤6 ppm) verified 7-day point prevalence abstinence. At baseline, the participants' mean (standard deviation) age was 21.06 (1.62) years. Most identified as daily smokers (57.9%, n = 158), consumed ≤10 cigarettes daily (89.4%, n = 244), and expressed low level of nicotine dependence as measured by Heaviness of Smoking Index score (86.1%, n = 235). Regarding intention-to-treat analyses, participants in the Quit with US intervention group achieved significantly greater smoking abstinence rate than those in the control group (58.4% (80/137) vs. 30.9% (42/136), risk ratio = 1.89, 95% confidence intervals = 1.42 to 2.52, p < 0.001). In conclusion, Quit with US integrated with pharmacists' smoking cessation counseling significantly enhanced smoking abstinence rates among young adult light smokers consuming ≤ 10 cigarettes daily.

Effect of a Lactobacillus fermentation product on postweaning heifer performance.

The objective of the experiment was to compare the effect of dietary inclusion of a prebiotic fermentation product of Lactobacillus acidophilus (LaP, RumaCell; 5 mL animal-1 d-1) or monensin on performance of replacement beef heifers. Heifers received a total mixed ration containing either LaP (n = 77) or monensin (MON; Rumensin; 200 mg animal-1 d-1; n = 79). Heifers were fed for 71 d in a GrowSafe unit, so individual feed intake could be measured. Heifers were weighed every 2 wk and feed efficiency calculated by residual feed intake (RFI). At the end of the RFI trial, heifers remained on their diets for an additional 27 d and were estrus synchronized using the 14-d CIDR + PG protocol and bred by artificial insemination (AI) followed by natural service. Prior to estrous synchronization, reproductive tract scores (RTS; 1 = infantile to 5 = cycling/presence of corpus luteum) were measured. Continuous variables were analyzed using generalized mixed models, whereas categorical data were analyzed by logistic regression. Body weights, average daily gain, feed intake, and RFI value were similar (P > 0.30) among MON- and LaP-supplemented heifers. Across treatments, heifers gained 0.9 ±â€…0.1 kg/d while consuming 9.3 ±â€…0.5 kg of diets daily. Reproductive development as indicated by RTS was similar (P > 0.28) between treatments. However, estrus response increased (P < 0.01) and AI pregnancy rates tended to be greater (P < 0.07) for MON compared to LaP heifers. In contrast, the percentage of heifers pregnant by 60 and 100 d (80.4% and 90.5%, respectively) was not different (P > 0.33) for MON and LaP heifers. In conclusion, addition of LaP to replacement heifer diets may result in growth and reproductive performance similar to an ionophore, if dietary energy is adequate for normal heifer growth.

Electronic Cigarette Use and Other Factors Associated with Cigarette Smoking among Thai Undergraduate Students.

The prevalence of smoking among young adults in Thailand has gradually increased. Therefore, this study aimed to identify factors associated with cigarette smoking among undergraduate students. This cross-sectional study used a self-administered, anonymous online questionnaire to gather data from undergraduate students across four universities in Chiang Mai Province, Thailand. All 1126 participants were an average age of 21.30 years old (SD 1.48). The findings revealed seven factors significantly associated with cigarette smoking (p < 0.05), including male sex, having no medical conditions, consuming alcohol daily and consuming alcohol in the past, having brothers or sisters who smoked cigarettes, having a father or mother who smoked cigarettes, having parents who considered smoking acceptable and having parents who had uncertain concerns about smoking, and had or have used electronic cigarettes (e-cigarettes). These associated factors could be useful in implementing appropriate tobacco-control programs to prevent cigarette smoking among undergraduate students. Relevant organizations, universities and healthcare professionals should communicate correct and appropriate information about the illness and diseases caused by using tobacco products to strengthen the correct perceptions of the harms of cigarette smoking and e-cigarette use among undergraduate students. Furthermore, smoke-free policies should be monitored and strictly enforced, particularly in university areas.

Factors Associated with the Dual Use of Electronic Cigarettes and Cigarettes among Thai Undergraduate Students Who Smoked Cigarettes.

This study proposed to identify factors associated with the dual use of electronic cigarettes (e-cigarettes) and cigarettes among undergraduate students who smoked cigarettes. This cross-sectional study employed a self-administered, anonymous online questionnaires to collect information from undergraduate smokers in northern Thailand. Of the 494 participants, 82.8% were dual users of e-cigarettes and cigarettes. The two main reasons for using e-cigarettes were an absence of cigarette smoke odor (76.8%) and availability of flavors (70.7%). Undergraduate smokers who initiated smoking at ≥18 years old were more likely to be dual users than those who initiated smoking at younger age (adjusted odds ratio [aOR]: 2.79, 95% confidence intervals [CI]: 1.32-5.89, p = 0.007). Undergraduate smokers who smoked ≥11 cigarettes daily were more likely to be dual users than those who smoked less (aOR: 2.64, 95% CI: 1.52-4.61, p = 0.001). Conversely, undergraduate smokers who had attempted to quit during the past year were less likely to be dual users (aOR: 0.26, 95% CI: 0.12-0.56, p = 0.001). In conclusion, dual use of e-cigarettes and cigarettes among undergraduate smokers was associated with older age at cigarette smoking initiation, a higher number of cigarettes smoked daily, and having no past year's cigarette quit attempts.

Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.

Feasibility of a Smoking Cessation Smartphone App (Quit with US) for Young Adult Smokers: A Single Arm, Pre-Post Study.

While smartphone applications (apps) have been shown to enhance success with smoking cessation, no study has been conducted among young adult smokers aged 18-24 years in Thailand. Quit with US was developed based on the 5 A's model and self-efficacy theory. This single arm, pre-post study was conducted aiming to assess results after using Quit with US for 4 weeks. The primary outcome was a biochemically verified 7-day point prevalence of smoking abstinence. The secondary outcomes included smoking behaviors, knowledge and attitudes toward smoking and smoking cessation, and satisfaction and confidence in the smartphone app. A total number of 19 young adult smokers were included; most participants were males (68.4%) with the mean (SD) age of 20.42 (1.46) years. After 4 weeks of study, the primary outcome demonstrated a smoking cessation rate of 31.6%. All 19 participants expressed better smoking behaviors and better knowledge and attitudes toward smoking and smoking cessation. Further, they were satisfied with the smartphone app design and content and expressed confidence in using it. These findings provided preliminary evidence that Quit with US was found to be a potentially effective smoking cessation smartphone app for young adult smokers.

Chronic Antidiabetic Actions of Leptin: Evidence From Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor.

We used parabiosis to determine whether the central nervous system (CNS)-mediated antidiabetic effects of leptin are mediated by release of brain-derived circulating factors. Parabiosis was surgically induced at 4 weeks of age, and an intracerebroventricular (ICV) cannula was placed in the lateral cerebral ventricle at 12 weeks of age for ICV infusion of leptin or saline vehicle. Ten days after surgery, food intake, body weight, and blood glucose were measured for 5 consecutive days, and insulin-deficiency diabetes was induced in all rats by a single streptozotocin (STZ) injection (40 mg/kg). Five days after STZ injection, leptin or vehicle was infused ICV for 7 days, followed by 5-day recovery period. STZ increased blood glucose and food intake. Chronic ICV leptin infusion restored normoglycemia in leptin-infused rats while reducing blood glucose by ∼27% in conjoined vehicle-infused rats. This glucose reduction was caused mainly by decreased hepatic gluconeogenesis. Chronic ICV leptin infusion also reduced net cumulative food intake and increased GLUT4 expression in skeletal muscle in leptin/vehicle compared with vehicle/vehicle conjoined rats. These results indicate that leptin's CNS-mediated antidiabetic effects are mediated, in part, by release into the systemic circulation of leptin-stimulated factors that enhance glucose utilization and reduce liver gluconeogenesis.

Psychotropic medicine prescribing and polypharmacy for people with dementia entering residential aged care: the influence of changing general practitioners.

OBJECTIVE: To examine relationships between changing general practitioner after entering residential aged care and overall medicines prescribing (including polypharmacy) and that of psychotropic medicines in particular. DESIGN: Retrospective data linkage study. SETTING, PARTICIPANTS: 45 and Up Study participants in New South Wales with dementia who were PBS concession card holders and entered permanent residential aged care during January 2010 - June 2014 and were alive six months after entry. MAIN OUTCOME MEASURES: Inverse probability of treatment-weighted numbers of medicines dispensed to residents and proportions of residents dispensed antipsychotics, benzodiazepines, and antidepressants in the six months after residential care entry, by most frequent residential care GP category: usual (same as during two years preceding entry), known (another GP, but known to the resident), or new GP. RESULTS: Of 2250 new residents with dementia (mean age, 84.1 years; SD, 7.0 years; 1236 women [55%]), 625 most frequently saw their usual GPs (28%), 645 saw known GPs (29%), and 980 saw new GPs (44%). The increase in mean number of dispensed medicines after residential care entry was larger for residents with new GPs (+1.6 medicines; 95% CI, 1.4-1.9 medicines) than for those attended by their usual GPs (+0.7 medicines; 95% CI, 0.4-1.1 medicines; adjusted rate ratio, 2.42; 95% CI, 1.59-3.70). The odds of being dispensed antipsychotics (adjusted odds ratio [aOR], 1.59; 95% CI, 1.18-2.12) or benzodiazepines (aOR, 1.69; 95% CI, 1.25-2.30), but not antidepressants (aOR, 1.32; 95% CI, 0.98-1.77), were also higher for the new GP group. Differences between the known and usual GP groups were not statistically significant. CONCLUSIONS: Increases in medicine use and rates of psychotropic dispensing were higher for people with dementia who changed GP when they entered residential care. Facilitating continuity of GP care for new residents and more structured transfer of GP care may prevent potentially inappropriate initiation of psychotropic medicines.

Dimethyl fumarate preserves left ventricular infarct integrity following myocardial infarction via modulation of cardiac macrophage and fibroblast oxidative metabolism.

Myocardial infarction (MI) is one of the leading causes of mortality and cardiovascular disease worldwide. MI is characterized by a substantial inflammatory response in the infarcted left ventricle (LV), followed by transition of quiescent fibroblasts to active myofibroblasts, which deposit collagen to form the reparative scar. Metabolic shifting between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is an important mechanism by which these cell types transition towards reparative phenotypes. Thus, we hypothesized that dimethyl fumarate (DMF), a clinically approved anti-inflammatory agent with metabolic actions, would improve post-MI remodeling via modulation of macrophage and fibroblast metabolism. Adult male C57BL/6J mice were treated with DMF (10 mg/kg) for 3-7 days after MI. DMF attenuated LV infarct and non-infarct wall thinning at 3 and 7 days post-MI, and decreased LV dilation and pulmonary congestion at day 7. DMF improved LV infarct collagen deposition, myofibroblast activation, and angiogenesis at day 7. DMF also decreased pro-inflammatory cytokine expression (Tnf) 3 days after MI, and decreased inflammatory markers in macrophages isolated from the infarcted heart (Hif1a, Il1b). In fibroblasts extracted from the infarcted heart at day 3, RNA-Seq analysis demonstrated that DMF promoted an anti-inflammatory/pro-reparative phenotype. By Seahorse analysis, DMF did not affect glycolysis in either macrophages or fibroblasts at day 3, but enhanced macrophage OXPHOS while impairing fibroblast OXPHOS. Our results indicate that DMF differentially affects macrophage and fibroblast metabolism, and promotes anti-inflammatory/pro-reparative actions. In conclusion, targeting cellular metabolism in the infarcted heart may be a promising therapeutic strategy.

Direct Cardiac Actions of the Sodium Glucose Co-Transporter 2 Inhibitor Empagliflozin Improve Myocardial Oxidative Phosphorylation and Attenuate Pressure-Overload Heart Failure.

Background We determined if the sodium glucose co-transporter 2 inhibitor empagliflozin attenuates pressure overload-induced heart failure in non-diabetic mellitus mice by direct cardiac effects and the mechanisms involved. Methods and Results Male C57BL/6J mice (4-6 months of age) were subjected to sham surgeries or transverse aortic constriction to produce cardiac pressure overload. Two weeks after transverse aortic constriction, empagliflozin (10 mg/kg per day) or vehicle was administered daily for 4 weeks. Empagliflozin increased survival rate and significantly attenuated adverse left ventricle remodeling and cardiac fibrosis after transverse aortic constriction. Empagliflozin also attenuated left ventricular systolic and diastolic dysfunction, evaluated by echocardiography, and increased exercise endurance by 36% in mice with transverse aortic constriction-induced heart failure. Empagliflozin significantly increased glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. These beneficial cardiac effects of empagliflozin occurred despite no significant changes in fasting blood glucose, body weight, or daily urine volume. In vitro experiments in isolated cardiomyocytes indicated that empagliflozin had direct effects to improve cardiomyocyte contractility and calcium transients. Importantly, molecular docking analysis and isolated perfused heart experiments indicated that empagliflozin can bind cardiac glucose transporters to reduce glycolysis, restore activation of adenosine monophosphate-activated protein kinase and inhibit activation of the mammalian target of rapamycin complex 1 pathway. Conclusions Our study demonstrates that empagliflozin may directly bind glucose transporters to reduce glycolysis, rebalance coupling between glycolysis and oxidative phosphorylation, and regulate the adenosine monophosphate-activated protein kinase mammalian target of rapamycin complex 1 pathway to attenuate adverse cardiac remodeling and progression of heart failure induced by pressure-overload in non-diabetic mellitus mice.

Interaction of Obesity and Hypertension on Cardiac Metabolic Remodeling and Survival Following Myocardial Infarction.

Background Obesity and hypertension are risk factors for myocardial infarction (MI); however, their potential interactions on post-MI outcomes are unclear. We examined interactions of obesity and hypertensionon post-MI function, remodeling, metabolic changes, and recovery. Methods and Results Male and female C57BL/6J mice were provided standard chow or high-fat/fructose diet for 8 weeks and then infused with angiotensin II for 2 weeks to induce hypertension. MI was then induced by surgical ligation of the left coronary artery for 7 days. Obesity alone did not cause cardiac injury or exacerbate hypertension-induced cardiac dysfunction. After MI, however, obese-normotensive mice had lower survival rates compared with chow-fed mice (56% versus 89% males; 54% versus 75% females), which were further decreased by hypertension (29% males; and 35% females). Surviving obese-normotensive males displayed less left ventricular dilation and pulmonary congestion compared with chow-fed males after MI; hypertension reversed left ventricular dilation because of high-fat/fructose diet and promoted significant pulmonary congestion compared with chow-fed controls. Obese-normotensive males displayed higher left ventricular α-MHC (alpha-myosin heavy chain) protein, phosphorylated Akt (protein kinase B) and AMPK (adenosine-monophosphate activated kinase), PPAR-γ (peroxisome proliferator activated receptor gamma), and plasma adiponectin levels after MI, indicating favorable contractile and metabolic changes. However, these favorable contractile and metabolic changes were attenuated by hypertension. Obese-hypertensive males also had lower levels of collagen in the infarcted region, indicating decreased ability to promote an adaptive wound healing response to MI. Conclusions Obesity reduces post-MI survival but is associated with improved post-MI cardiac function and metabolism in surviving normotensive mice. When hypertension accompanies obesity, favorable metabolic pathways associated with obesity are attenuated and post-MI cardiac function and remodeling are adversely impacted.

Restoration of Cardiac Function After Myocardial Infarction by Long-Term Activation of the CNS Leptin-Melanocortin System.

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca2+ coupling, and mitochondrial efficiency. These findings highlight a potentially novel therapeutic approach for myocardial infarction and heart failure.