Publications by authors named "Mohammad Keykhaei"
Introduction: Macrophages (MΦ) modulate both myocardial inflammatory and reparative phases following ischemia-reperfusion (I/R) injury. The mechanistic target of rapamycin (mTOR) is thought to play an important role in MΦ phenotype and functionality, but studies report conflicting net influences suggesting dependence on disease context and downstream signaling. Here, we tested the impact of MΦ with constitutive mTORC1 activation induced by targeted deletion of tuberous sclerosis complex 2 (TSC2) on cardiac responses to I/R injury.
View Article and Find Full Text PDFATP-Citrate Lyase Supports Cardiac Function and NAD/NADH Balance and Is Depressed in Human Failing Myocardium.
JACC Basic Transl Sci
July 2025
ATP-citrate lyase (ACLY) regulates lipogenesis and cell proliferation, and forms a cytosolic TCA-bypass circuit impacting NADH. We show that acute and chronic ACLY inhibition in cardiomyocytes depresses the NAD/NADH ratio by increasing mitochondrial NADH. Acute suppression causes dose-dependent cytotoxicity, but at low doses augments aerobic respiration without impeding myocyte function.
View Article and Find Full Text PDFMyocardial Proteome in Human Heart Failure With Preserved Ejection Fraction.
J Am Heart Assoc
March 2025
Background: Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF but has few effective therapies. Recent human myocardial transcriptomics and metabolomics have identified major differences between HFpEF and controls. How this translates at the protein level is unknown.
View Article and Find Full Text PDFBackground: The optimal long-term antithrombotic strategy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains uncertain. Individual randomized controlled trials (RCTs) had variations in their reported results and were not powered for effectiveness outcomes.
Objectives: This study aimed to pool the results of RCTs comparing the effectiveness and safety of oral anticoagulation (OAC) monotherapy vs OAC plus single antiplatelet therapy (SAPT) in patients with AF and stable CAD.
Myocardial ultrastructure of human heart failure with preserved ejection fraction.
Nat Cardiovasc Res
August 2024
Article Synopsis
- * In patients with morbid obesity and HFpEF, there are notable changes in heart muscle cells, including disrupted calcium response, altered gene expression, and cellular structure issues.
- * Advanced imaging techniques revealed severe damage to heart muscle, particularly in the most obese patients, including mitochondrial dysfunction and reduced fatty acid processing, independent of diabetes.
Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) reflects half of all clinical HF yet has few therapies. Obesity and diabetes are now common comorbidities which have focused attention towards underlying myocardial metabolic defects. The profile of a major metabolic pathway, glycolytic intermediates and their regulating enzymes and ancillary pathways, remains unknown.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the prevalence and cardiovascular disease (CVD) risk of metabolically healthy obesity (MHO) in Iranian adults, finding that about 6.42% are classified as MHO.
- Nearly 25% of obese individuals, with a higher prevalence among men and women, showed MHO characteristics, and this group was younger than those with metabolically unhealthy obesity (MUO).
- Although MHO has a lower CVD risk compared to MUO, there is a possibility that individuals with MHO may transition to a less healthy state over time.
Background: ATP-citrate lyase (ACLY) converts citrate into acetyl-CoA and oxaloacetate in the cytosol. It plays a prominent role in lipogenesis and fat accumulation coupled to excess glucose, and its inhibition is approved for treating hyperlipidemia. In RNAseq analysis of human failing myocardium, we found ACLY gene expression is reduced; however the impact this might have on cardiac function and/or metabolism has not been previously studied.
View Article and Find Full Text PDFMortality and disability-adjusted life years in North Africa and Middle East attributed to kidney dysfunction: a systematic analysis for the Global Burden of Disease Study 2019.
Clin Kidney J
January 2024
Article Synopsis
- The study assessed the health impact of kidney dysfunction as a metabolic risk factor in 21 countries of the North Africa and Middle East region between 1990 and 2019, utilizing data from the Global Burden of Disease 2019 study.
- In 2019, kidney dysfunction led to approximately 296,632 deaths in the region, reflecting a significant increase since 1990, with countries like Afghanistan and Egypt showing the highest death rates associated with this condition.
- The findings highlighted the role of kidney dysfunction in contributing to various cardiovascular diseases, urging policymakers to enhance prevention and management strategies to mitigate its broader health implications.
Background: Hematologic malignancies have a great essential role in cancer global burden. Leukemia which two major subtypes based on the onset, is one of the common subtypes of this malignancy.
Method: For the GBD 2019 study, cancer registry data and vital registration system were used to estimate leukemia mortality.
Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of all heart failure world-wide and remains a major unmet medical need. The most effective recently approved treatments were first developed for diabetes, suggesting metabolic defects are paramount. Myocardial metabolomics in human HFpEF has identified reduced fatty acid and branched chain amino acid catabolism, but the status of glycolysis is unknown.
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- Lip, oral, and pharyngeal cancers pose significant global health challenges, making it essential to analyze their burden for effective health policies.
- The study utilized data from the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study to assess cancer incidence, mortality, and life years lost across 204 countries, linking these to socio-demographic factors.
- Findings revealed approximately 370,000 cases and 199,000 deaths for lip and oral cavity cancer, and 167,000 cases and 114,000 deaths for other pharyngeal cancers in 2019, with smoking being the leading risk factor for these cancers, especially in low and middle SDI regions.
Article Synopsis
- Chronic kidney disease (CKD) presents a substantial challenge globally, with over 18 million new cases in 2019 and concerns about the quality of care provided for this condition over the years.
- The study analyzed trends in CKD incidence and created a Quality of Care Index (QCI) to evaluate care quality across different regions, demographics, and ages, finding disparities, particularly favoring males and the European region.
- The findings highlight ongoing inequalities in CKD care and suggest that health policymakers should focus on improving care for minorities to enhance overall CKD management.
Article Synopsis
- Particulate matter (PM) pollution significantly contributes to cardiovascular diseases, with the study analyzing its impact from 1990 to 2019 using the Global Burden of Disease (GBD) data.
- Despite a 36.7% decline in deaths attributable to PM, total disability-adjusted life-years (DALYs) rose by 31% to 8.9 million in 2019, with men experiencing higher mortality rates than women.
- The findings highlight the need for targeted global health policies to address PM pollution, considering differences in gender and regional health disparities for better resource allocation and equity in healthcare access.
Article Synopsis
- The COVID-19 pandemic caused a shortage of ventilators, prompting health authorities to create guidelines for prioritizing patient care based on real-time resource availability and patient needs.
- The study analyzed data from 599,340 hospitalized adult patients, categorizing them by demographics and assessing their likelihood of requiring ventilation therapy.
- Two models were used: one to estimate the probability of receiving ventilation therapy and another to evaluate its clinical benefits across different patient groups, finding that 10% of participants received ventilation therapy during hospitalization.
Background: We aimed to estimate the prevalence of physical inactivity in all districts of Iran and the disparities between subgroups defined by various measures.
Methods: Small area estimation method was employed to estimate the prevalence of physical inactivity in districts based on the remaining districts in which data on the level of physical inactivity were available. Various comparisons on the estimations were done based on socioeconomic, sex, and geographical stratifications to determine the disparities of physical inactivity among districts of Iran.
Aims: To investigate the journey of patients with diabetes in the healthcare system using nationally-representative patient-reported data.
Methods: Participants were recruited using a machine-learning-based sampling method based on healthcare structures and medical outcome data and were followed up for three months. We assessed the resource utilization, direct/indirect costs, and quality of healthcare services.
Trends of national and sub-national burden attributed to kidney dysfunction risk factor in Iran: 1990-2019.
Front Endocrinol (Lausanne)
March 2023
Background: Kidney dysfunction is a risk factor for cardiovascular disease and chronic kidney disease. Herein, we aimed to describe the attributable burden of kidney dysfunction at the national and sub-national levels in Iran.
Methods: The Global Burden of Disease (GBD) 2019 data were extracted on the deaths, disability-adjusted life years (DALYs), years of life lost, and years lived with disability attributed to the risk factor of kidney dysfunction by age and sex at the national and provincial levels from 1990-2019.
Introduction: Data on the distribution of the burden of diseases is vital for policymakers for the appropriate allocation of resources. In this study, we report the geographical and time trends of chronic respiratory diseases (CRDs) in Iran from 1990 to 2019 based on the Global burden of the Disease (GBD) study 2019.
Methods: Data were extracted from the GBD 2019 study to report the burden of CRDs through disability-adjusted life years (DALYs), mortality, incidence, prevalence, Years of Life lost (YLL), and Years Lost to Disability (YLD).
Article Synopsis
- This study analyzes the burden of ischemic heart disease (IHD) in Iran from 1990 to 2019 to guide healthcare policy development.
- Findings revealed significant decreases in age-standardized death rates (42.7%) and disability-adjusted life years (DALYs) (47.7%), while incidence rates fell more slowly by only 7.7%.
- The main risk factors contributing to deaths and DALYs were high blood pressure and LDL cholesterol, stressing the need for improved prevention strategies and management of rising health risks like high fasting glucose and body mass index (BMI).
Article Synopsis
- Hypertension significantly contributes to the risk of developing cardiovascular diseases (CVD), and the study aimed to determine how this risk varies by age and sex among different blood pressure levels.
- Data from a large Iranian survey involving over 27,000 participants aged 25 and older was analyzed through four phases to calculate population attributable fraction (PAF) for CVD based on blood pressure classifications.
- Results showed that younger females had the highest PAF at elevated blood pressure levels, underscoring the need for targeted screening and improved access to blood pressure medications, especially for younger individuals.
Introduction: With the current high burden on the healthcare system and limited resources, the efficient utilization of facilities is of utmost importance. We sought to present the practice guideline used at a high prevalence tertiary cardiology center and compare its safety and efficacy performance with the single high-sensitivity cardiac troponin T strategy, conventional and modified HEART score.
Methods: In this prospective cohort study, consecutive patients presenting to the emergency department with chest pain or an angina equivalent were recruited.
Objectives: Updating burden data of chronic kidney disease (CKD) as one of the most prevalent non-communicable diseases is essential for proper provision of healthcare by policymakers. We aimed to estimate the burden of CKD and its attributed burden in North Africa and Middle East region (NAME) during 1990-2019.
Methods: The CKD-related Global Burden of Disease (GBD) 2019 estimates were extracted from Health Metrics and Evaluation (IHME) website.
Article Synopsis
- Bladder cancer is the second most common genitourinary cancer and is a significant cause of cancer-related deaths, highlighting the need for assessing the quality of care (QOC) for patients.
- Data from the Global Burden of Disease database was used to create a quality of care index (QCI) that reflects various healthcare metrics, showing a global increase in QCI scores from 75.7% in 1990 to 80.9% in 2019, although disparities exist based on region and socio-demographic indices.
- While the overall QCI has improved, significant gender disparities still persist, and higher socio-demographic index countries demonstrate better QOC, emphasizing the need for targeted improvements in lower SDI regions.