Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.

BACKGROUND: Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium. METHODS: We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2-) production by ESR spectroscopy, NF-κB binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice. RESULTS: Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2- generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-κB p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice. CONCLUSIONS: EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.

Targeting PCSK9 as a key player in lipid metabolism: exploiting the therapeutic and biosensing potential of aptamers.

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.

The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

The Pandemic of Coronary Heart Disease in the Middle East and North Africa: What Clinicians Need to Know.

PURPOSE OF REVIEW: Coronary heart disease (CHD) is the leading cause of morbidity, mortality, and disability in the Middle East and North Africa (MENA). While the prevention, diagnosis, and management of CHD have been detailed in international guidelines, we aimed in this review to quantify the pandemic of CHD in the MENA region and highlight regional patient characteristics, clinical challenges, and future directions to optimize CHD care in the region. RECENT FINDINGS: Patients with CHD in the MENA feature younger age at presentation and worse prognosis in women. Despite the high burden of CHD risk factors, many of these factors remain underrecognized, undertreated, and uncontrolled. Additionally, CHD care is hampered by poor patient awareness, inefficient preventive strategies, and limited access to guideline-recommended therapeutics. All stakeholders involved in healthcare should work together to develop and execute strategies aimed at tackling the burden of CHD in the MENA.

A cross-sectional study of the prevalence and clinical management of atherosclerotic cardiovascular diseases in patients with type 2 diabetes across the Middle East and Africa (PACT-MEA): Study design and rationale.

AIM: To investigate the epidemiology and clinical management of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (eASCVD) or high/very high ASCVD risk, defined by the 2021 European Society of Cardiology Guidelines, in seven countries in the Middle East and Africa (PACT-MEA; NCT05317845), and to assess physicians' attitudes and the basis for their decision-making in the management of these patients. MATERIALS AND METHODS: PACT-MEA is a cross-sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D. RESULTS: The primary and secondary objectives are to determine the prevalence of eASCVD and high/very high ASCVD risk in patients with T2D. Current treatment with cardioprotective antidiabetic medication, the proportion of patients meeting the treatment criteria for reimbursement in the study countries where there is an applicable reimbursement guideline, and physician-reported factors in clinical decision-making in T2D management, will also be assessed. CONCLUSIONS: This large cross-sectional study will establish the estimated prevalence and management of eASCVD and high/very high ASCVD risk in patients with type 2 diabetes across the Middle East and Africa.

Outcomes of Left Main Revascularization in Patients with Anemia: Gulf Left Main Registry.

INTRODUCTION: The aim of this study was to evaluate the effects of baseline anemia and anemia following revascularization on outcomes in patients with unprotected left main coronary artery (ULMCA) disease. METHODS: This was a retrospective, multicenter, observational study conducted between January 2015 and December 2019. The data on patients with ULMCA who underwent revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were stratified by the hemoglobin level at baseline into anemic and non-anemic groups to compare in-hospital events. The pre-discharge hemoglobin following revascularization was categorized into very low (<80 g/L for men and women), low (≥80 and ≤119 g/L for women and ≤129 g/L for men), and normal (≥130 g/L for men and ≥120 g/L for women) to assess impact on follow-up outcomes. RESULTS: A total of 2,138 patients were included, 796 (37.2%) of whom had anemia at baseline. A total of 319 developed anemia after revascularization and moved from being non-anemic at baseline to anemic at discharge. There was no difference in hospital major adverse cardiac and cerebrovascular event (MACCE) and mortality between CABG and PCI in anemic patients. At a median follow-up time of 20 months (interquartile range [IQR]: 27), patients with pre-discharge anemia who underwent PCI had a higher incidence of congestive heart failure (CHF) (p < 0.0001), and those who underwent CABG had significantly higher follow-up mortality (HR: 9.85 (95% CI: 2.53-38.43), p = 0.001). CONCLUSION: In this Gulf LM study, baseline anemia had no impact upon in-hospital MACCE and total mortality following revascularization (PCI or CABG). However, pre-discharge anemia is associated with worse outcomes after ULMCA disease revascularization, with significantly higher all-cause mortality in patients who had CABG, and a higher incidence of CHF in PCI patients, at a median follow-up time of 20 months (IQR: 27).

High prevalence of cardiometabolic risk factors amongst young adults in the United Arab Emirates: the UAE Healthy Future Study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the world. In the United Arab Emirates (UAE), it accounts for 40% of mortality. CVD is caused by multiple cardiometabolic risk factors (CRFs) including obesity, dysglycemia, dyslipidemia, hypertension and central obesity. However, there are limited studies focusing on the CVD risk burden among young Emirati adults. This study investigates the burden of CRFs in a sample of young Emiratis, and estimates the distribution in relation to sociodemographic and behavioral determinants. METHODS: Data was used from the baseline data of the UAE Healthy Future Study volunteers. The study participants were aged 18 to 40 years. The study analysis was based on self-reported questionnaires, anthropometric and blood pressure measurements, as well as blood analysis. RESULTS: A total of 5167 participants were included in the analysis; 62% were males and the mean age of the sample was 25.7 years. The age-adjusted prevalence was 26.5% for obesity, 11.7% for dysglycemia, 62.7% for dyslipidemia, 22.4% for hypertension and 22.5% for central obesity. The CRFs were distributed differently when compared within social and behavioral groups. For example, obesity, dyslipidemia and central obesity in men were found higher among smokers than non-smokers (p < 0.05). And among women with lower education, all CRFs were reported significantly higher than those with higher education, except for hypertension. Most CRFs were significantly higher among men and women with positive family history of common non-communicable diseases. CONCLUSIONS: CRFs are highly prevalent in the young Emirati adults of the UAE Healthy Future Study. The difference in CRF distribution among social and behavioral groups can be taken into account to target group-specific prevention measures.

Left Main Coronary Artery Revascularization in Patients with Impaired Renal Function: Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting.

INTRODUCTION: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. METHODS: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19-15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79-3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71-1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90-1.39], p = 0.312). CONCLUSIONS: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.

Association of obesity indices with in-hospital and 1-year mortality following acute coronary syndrome.

BACKGROUND/OBJECTIVES: According to the "obesity paradox", adults with obesity have a survival advantage following acute coronary syndrome, compared with those without obesity. Previous studies focused on peripheral obesity and whether this advantage is conferred by central obesity is unknown. The objective of this study was to describe the association of peripheral and central obesity indices with risk of in-hospital and 1-year mortality following acute coronary syndrome (ACS). SUBJECTS/METHODS: Gulf COAST is a prospective ACS registry that enrolled 4044 patients age ≥18 years from January 2012 through January 2013, across 29 hospitals in four Middle Eastern countries. Associations of indices of peripheral obesity (body-mass index, [BMI]) and central obesity (waist circumference [WC] and waist-to-height ratio [WHtR]) with mortality following ACS were analyzed in logistic regression models (odds ratio, 95% CI) with and without adjustment for Global Registry of Acute Coronary Events risk score. RESULTS: Of 3882 patients analyzed (mean age: 60 years; 33.3% women [n = 1294]), the prevalence of obesity was 34.5% (BMI ≥ 30.0 kg/m2), 72.2% (WC ≥ 94.0 cm [men] or ≥80.0 cm [women]) and 90.0% (WHtR ≥ 0.5). In adjusted models, deciles of obesity indices showed higher risk of mortality at extreme versus intermediate deciles (U-shaped). When defined by conventional cut-offs, peripheral obesity (BMI ≥ 30.0 versus 18.5-29.9 kg/m2) showed inverse association with risk of in-hospital mortality (0.64; 95% CI, 0.42-0.99; P = 0.04; central obesity showed trend toward reduced mortality). In contrast, for risk of 1-year mortality, all indices showed inverse association. Obesity, defined by presence of all three indices, versus nonobesity showed inverse association with risk of 1-year mortality (0.52; 95% CI, 0.35-0.75; P = 0.001). Results were similar among men and women. CONCLUSION: The degree of obesity paradox following ACS depends on the obesity index and follow-up time. Obesity indices may aid in risk stratification of mortality following ACS.

The role of renin-angiotensin system activated phagocytes in the SARS-CoV-2 coronavirus infection.

OBJECTIVE: Management of the pandemic caused by the novel coronavirus SARS-CoV-2 challenges both scientists and physicians to rapidly develop, and urgently assess, effective diagnostic tests and therapeutic interventions. The initial presentation of the disease in symptomatic patients is invariably respiratory, with dry cough being the main symptom, but an increasing number of reports reveal multiple-organ involvement. The aim of this review is to summarize the potential role of the renin-angiotensin system activated phagocytes in the pathogenesis of COVID-19 disease. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "SARS," "COVID-19," "renin-angiotensin-system," "phagocyte," "reactive free radical," "antioxidant," "ARDS," "thrombosis," "myocardial," "ischaemia," "reperfusion," "microvascular," and "ACE2." Abstracts and reports from meetings were not included in this work. Only articles published in English between 1976 and 2020 were reviewed. RESULTS: The cellular target of SARS viruses is the angiotensin-converting enzyme 2, a critical regulating protein in the renin-angiotensin system. The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst. In the case of an overstimulated host immune response, not only devastating respiratory symptoms but even systemic or multiorgan involvement may be observed. CONCLUSIONS: Early-stage medical interventions may assist in returning the exaggerated immune response to a normal range; however, some therapeutic delay might result in excessive tissue damages, occasionally mimicking a systemic disease with a detrimental outcome.

Impact of Dual versus Single Antiplatelet Therapy on Major Cardiovascular Outcomes in Patients with Acute Coronary Syndrome in the Arabian Gulf.

OBJECTIVE: To evaluate the association of dual versus single antiplatelet therapy with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. SUBJECTS AND METHODS: Data were analyzed from 3,559 patients with a diagnosis of ACS admitted to 29 hospitals in 4 Arabian Gulf countries (Bahrain, Kuwait, Oman, and United Arab Emirates) from January 2012 to January 2013. Dual antiplatelet therapy (DAPT), consisting of aspirin and clopidogrel, was compared to aspirin alone. MACE included 12-months cumulative stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons, post discharge. Analyses were performed using multivariable logistic regression. RESULTS: A total of 74% (n = 2,634) of the patients were on DAPT. At 12-month follow-up, patients on DAPT were significantly less likely to experience MACE events (adjusted OR [aOR] 0.73; 95% CI: 0.61-0.86; p < 0.001). Lower cardiovascular (CV) event rates were also consistent across the following MACE components; MI (aOR 0.66; 95% CI: 0.49-0.88; p = 0.005), all-cause mortality (aOR 0.69; 95% CI: 0.51-0.94; p = 0.018), and readmissions for cardiac reasons (aOR 0.79; 95% CI: 0.66-0.95; p = 0.011). Conversely, DAPT was adversely associated with increased risk of stroke/TIA (aOR 1.68; 95% CI: 1.05-2.69; p = 0.030). CONCLUSIONS: DAPT, compared to aspirin therapy alone, was generally associated with better CV outcomes after an ACS event. However, DAPT was adversely associated with increased risk of stroke/TIA in ACS patients in the Arabian Gulf.

Precipitating Factors for Hospitalization with Heart Failure: Prevalence and Clinical Impact Observations from the Gulf CARE (Gulf aCute heArt failuRe rEgistry).

OBJECTIVE: Despite the expanding burden of heart failure (HF) worldwide, data on HF precipitating factors (PFs) in developing countries, particularly the Middle East, are very limited. We examined PFs in patients hospitalized with acute HF in a prospective multicenter HF registry from 7 countries in the Middle East. METHOD: Data were derived from the Gulf CARE (Gulf aCute heArt failuRe rEgistry) for a prospective, multinational, multicenter study of consecutive patients hospitalized with HF in 47 hospitals in 7 Middle Eastern countries between February 2012 and November 2012. PFs were determined by the treating physician from a predefined list at the time of hospitalization. RESULTS: The study included 5,005 patients hospitalized with acute HF, 2,276 of whom (45.5%) were hospitalized with acute new-onset HF (NOHF) and 2,729 of whom (54.5%) had acute decompensated chronic HF (DCHF). PFs were identified in 4,319 patients (86.3%). The most common PF in the NOHF group was acute coronary syndromes (ACS) (39.2%). In the DCHF group, it was noncompliance with medications (27.8%). Overall, noncompliance with medications was associated with a lower inhospital mortality (OR 0.47; 95% CI 0.28-0.80; p = 0.005) but a higher 1-year mortality (OR 1.43; 95% CI 1.1-1.85; p = 0.007). ACS was associated with higher inhospital mortality (OR 1.84; 95% CI 1.26-2.68; p = 0.002) and higher 1-year mortality (OR 1.62; 95% CI 1.27-2.06; p = 0.001). CONCLUSION: Preventive and therapeutic interventions specifically directed at noncompliance with medications and ACS are warranted in our region.

Randomized controlled trial of influenza vaccine in patients with heart failure to reduce adverse vascular events (IVVE): Rationale and design.

BACKGROUND: Influenza is associated with an increase in the risk of cardiac and other vascular events. Observational data and small randomized trials suggest that influenza vaccination may reduce such adverse vascular events. RESEARCH DESIGN AND METHODS: In a randomized controlled trial patients with heart failure are randomized to receive either inactivated influenza vaccine or placebo annually for 3 years. Patients aged ≥18 years with a clinical diagnosis of heart failure and NYHA functional class II, III and IV are eligible. Five thousand patients from 10 countries where influenza vaccination is not common (Asia, the Middle East, and Africa) have been enrolled. The primary outcome is a composite of the following: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalizations for heart failure using standardized criteria. Analyses will be based on comparing event rates between influenza vaccine and control groups and will include time to event, rate comparisons using Poisson methods, and logistic regression. The analysis will be conducted by intention to treat i.e. patients will be analyzed in the group in which they were assigned. Multivariable secondary analyses to assess whether variables such as age, sex, seasonality modify the benefits of vaccination are also planned for the primary outcome. CONCLUSION: This is the largest randomized trial to test if influenza vaccine compared to control reduces adverse vascular events in high risk individuals. TRIAL REGISTRATION NUMBER: Clinicaltrials.govNCT02762851.

Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study.

BACKGROUND: Atrial fibrillation is an important cause of morbidity and mortality worldwide, but scant data are available for long-term outcomes in individuals outside North America or Europe, especially in primary care settings. METHODS: We did a cohort study using a prospective registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis. 15 400 individuals were enrolled to determine the occurrence of death and strokes (the primary outcomes) in this cohort over eight geographical regions (North America, western Europe, and Australia; South America; eastern Europe; the Middle East and Mediterranean crescent; sub-Saharan Africa; India; China; and southeast Asia) 1 year after attending the emergency department. Patients from North America, western Europe, and Australia were used as the reference population, and compared with patients from the other seven regions FINDINGS: Between Dec 24, 2007, and Oct 21, 2011, we enrolled 15 400 individuals to the registry. Follow-up was complete for 15 361 (99·7%), of whom 1758 (11%) died within 1 year. Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis (377 [6%] of 6825 patients vs 1381 [16%] of 8536, p<0·0001). Twice as many patients had died by 1 year in South America (192 [17%] of 1132) and Africa (225 [20%] of 1137) compared with North America, western Europe, and Australia (366 [10%] of 3800, p<0·0001). Heart failure was the most common cause of death (519 [30%] of 1758); stroke caused 148 (8%) deaths. 604 (4%) of 15361 patients had had a stroke by 1 year; 170 (3%) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 (5%) of 8536 for whom it was a secondary diagnosis (p<0·0001). The highest number of strokes occurred in patients in Africa (89 [8%] of 1137), China (143 [7%] of 2023), and southeast Asia (88 [7%] of 1331) and the lowest occurred in India (20 [<1%] of 2536). 94 (3%) of 3800 patients in North America, western Europe, and Australia had a stroke. INTERPRETATION: Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important. Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation. FUNDING: Boehringer Ingelheim.

Coronary Heart Disease in the Middle East and North Africa: Current Status and Future Goals.

PURPOSE OF REVIEW: The Middle East and North Africa has witnessed a dramatic transformation over the last 30 years caused by rapid urbanization and modernization and significant changes to diet and lifestyle. This review attempts to highlight recent data in regards to ischemic heart disease and its risk factors from the region. RECENT FINDINGS: Ischemic heart disease is now the leading cause of death in the region. Age at presentation with myocardial infarction and acute coronary syndrome appears to be significantly younger than global averages. Increased rates of all major risk factors including diabetes, hypertension, hyperlipidemia, smoking, obesity, and sedentary lifestyle have been noted. Specifically, significant changes to dietary habits and growing epidemic of use of alternative tobacco products are noted. This review article highlights the growing epidemic of ischemic heart disease in the region led by dramatic increases in incidence of its risk factors. This epidemic will require a multipronged approach to address the varied issues and mitigate the growing prevalence of the disease.

The protective effects of statins in traumatic brain injury.

Traumatic brain injury (TBI), often referred to as the "silent epidemic", is the most common cause of mortality and morbidity worldwide among all trauma-related injuries. It is associated with considerable personal, medical, and economic consequences. Although remarkable advances in therapeutic approaches have been made, current treatments and clinical management for TBI recovery still remain to be improved. One of the factors that may contribute to this gap is that existing therapies target only a single event or pathology. However, brain injury after TBI involves various pathological mechanisms, including inflammation, oxidative stress, blood-brain barrier (BBB) disruption, ionic disturbance, excitotoxicity, mitochondrial dysfunction, neuronal necrosis, and apoptosis. Statins have several beneficial pleiotropic effects (anti-excitotoxicity, anti-inflammatory, anti-oxidant, anti-thrombotic, immunomodulatory activity, endothelial and vasoactive properties) in addition to promoting angiogenesis, neurogenesis, and synaptogenesis in TBI. Supposedly, using agents such as statins that target numerous and diverse pathological mechanisms, may be more effective than a single-target approach in TBI management. The current review was undertaken to investigate and summarize the protective mechanisms of statins against TBI. The limitations of conducted studies and directions for future research on this potential therapeutic application of statins are also discussed.