Cohort profile: the British Columbia COVID-19 Cohort (BCC19C)-a dynamic, linked population-based cohort.

Purpose: The British Columbia COVID-19 Cohort (BCC19C) was developed from an innovative, dynamic surveillance platform and is accessed/analyzed through a cloud-based environment. The platform integrates recently developed provincial COVID-19 datasets (refreshed daily) with existing administrative holdings and provincial registries (refreshed weekly/monthly). The platform/cohort were established to inform the COVID-19 response in near "real-time" and to answer more in-depth epidemiologic questions. Participants: The surveillance platform facilitates the creation of large, up-to-date analytic cohorts of people accessing COVID-19 related services and their linked medical histories. The program of work focused on creating/analyzing these cohorts is referred to as the BCC19C. The administrative/registry datasets integrated within the platform are not specific to COVID-19 and allow for selection of "control" individuals who have not accessed COVID-19 services. Findings to date: The platform has vastly broadened the range of COVID-19 analyses possible, and outputs from BCC19C analyses have been used to create dashboards, support routine reporting and contribute to the peer-reviewed literature. Published manuscripts (total of 15 as of July, 2023) have appeared in high-profile publications, generated significant media attention and informed policy and programming. In this paper, we conducted an analysis to identify sociodemographic and health characteristics associated with receiving SARS-CoV-2 laboratory testing, testing positive, and being fully vaccinated. Other published analyses have compared the relative clinical severity of different variants of concern; quantified the high "real-world" effectiveness of vaccines in addition to the higher risk of myocarditis among younger males following a 2nd dose of an mRNA vaccine; developed and validated an algorithm for identifying long-COVID patients in administrative data; identified a higher rate of diabetes and healthcare utilization among people with long-COVID; and measured the impact of the pandemic on mental health, among other analyses. Future plans: While the global COVID-19 health emergency has ended, our program of work remains robust. We plan to integrate additional datasets into the surveillance platform to further improve and expand covariate measurement and scope of analyses. Our analyses continue to focus on retrospective studies of various aspects of the COVID-19 pandemic, as well as prospective assessment of post-acute COVID-19 conditions and other impacts of the pandemic.

Visible minority status and occupation were associated with increased COVID-19 infection in Greater Vancouver British Columbia between June and November 2020: an ecological study.

Background: The COVID-19 pandemic has highlighted health disparities, especially among specific population groups. This study examines the spatial relationship between the proportion of visible minorities (VM), occupation types and COVID-19 infection in the Greater Vancouver region of British Columbia, Canada. Methods: Provincial COVID-19 case data between June 24, 2020, and November 7, 2020, were aggregated by census dissemination area and linked with sociodemographic data from the Canadian 2016 census. Bayesian spatial Poisson regression models were used to examine the association between proportion of visible minorities, occupation types and COVID-19 infection. Models were adjusted for COVID-19 testing rates and other sociodemographic factors. Relative risk (RR) and 95% Credible Intervals (95% CrI) were calculated. Results: We found an inverse relationship between the proportion of the Chinese population and risk of COVID-19 infection (RR = 0.98 95% CrI = 0.96, 0.99), whereas an increased risk was observed for the proportions of the South Asian group (RR = 1.10, 95% CrI = 1.08, 1.12), and Other Visible Minority group (RR = 1.06, 95% CrI = 1.04, 1.08). Similarly, a higher proportion of frontline workers (RR = 1.05, 95% CrI = 1.04, 1.07) was associated with higher infection risk compared to non-frontline. Conclusion: Despite adjustments for testing, housing, occupation, and other social economic status variables, there is still a substantial association between the proportion of visible minorities, occupation types, and the risk of acquiring COVID-19 infection in British Columbia. This ecological analysis highlights the existing disparities in the burden of diseases among different visible minority populations and occupation types.

The role of epicardial adipose tissue dysfunction in cardiovascular diseases: an overview of pathophysiology, evaluation, and management.

In recent decades, the epicardial adipose tissue (EAT) has been at the forefront of scientific research because of its diverse role in the pathogenesis of cardiovascular diseases (CVDs). EAT lies between the myocardium and the visceral pericardium. The same microcirculation exists both in the epicardial fat and the myocardium. Under physiological circumstances, EAT serves as cushion and protects coronary arteries and myocardium from violent distortion and impact. In addition, EAT acts as an energy lipid source, thermoregulator, and endocrine organ. Under pathological conditions, EAT dysfunction promotes various CVDs progression in several ways. It seems that various secretions of the epicardial fat are responsible for myocardial metabolic disturbances and, finally, leads to CVDs. Therefore, EAT might be an early predictor of CVDs. Furthermore, different non-invasive imaging techniques have been proposed to identify and assess EAT as an important parameter to stratify the CVD risk. We also present the potential therapeutic possibilities aiming at modifying the function of EAT. This paper aims to provide overview of the potential role of EAT in CVDs, discuss different imaging techniques to assess EAT, and provide potential therapeutic options for EAT. Hence, EAT may represent as a potential predictor and a novel therapeutic target for management of CVDs in the future.

COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, of which cardiovascular system diseases are one of the main manifestations, such as myocarditis, myocardial infarction, and arrhythmia, which threaten the infected population worldwide. These diseases threaten the cardiovascular health of infected populations worldwide. Although the prevalence of coronavirus disease 2019 (COVID-19) has slightly improved with virus mutation and population vaccination, chronic infection, post-infection sequelae, and post-infection severe disease patients still exist, and it is still relevant to study the mechanisms linking COVID-19 to cardiovascular disease (CVD). This article introduces the pathophysiological mechanism of COVID-19-mediated cardiovascular disease and analyzes the mechanism and recent progress of the interaction between SARS-CoV-2 and the cardiovascular system from the roles of angiotensin-converting enzyme 2 (ACE2), cellular and molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, and psychosocial factors, respectively. We also discussed the differences and mechanisms involved in cardiovascular system diseases combined with neocoronavirus infection in different populations and provided a theoretical basis for better disease prevention and management.

British Columbia's COVID-19 surveys on population experiences, action, and knowledge (SPEAK): methods and key findings from two large cross-sectional online surveys.

OBJECTIVES: To describe the methodology and key findings of British Columbia's (BC) COVID-19 SPEAK surveys, developed to understand the experiences, knowledge, and impact of the COVID-19 pandemic on British Columbians. METHODS: Two province-wide, cross-sectional, web-based population health surveys were conducted one year apart (May 2020 and April/May 2021). Questions were drawn from validated sources grounded within the social determinants of health to assess COVID-19 testing and prevention; mental and physical health; risk and protective factors; and healthcare, social, and economic impacts during the pandemic. Quota-based non-probability sampling by geography was applied to recruit a representative sample aged 18 years and older. Recruitment included strategic outreach and longitudinal follow-up of a subgroup of respondents from round one to round two. Post-collection weighting using Census data by age, sex, education, ethnicity, and geography was conducted. RESULTS: Participants included 394,382 and 188,561 British Columbians for the first and second surveys, respectively, including a longitudinal subgroup of 141,728. Key findings showed that societal impacts, both early in the pandemic and one year later, were inequitably distributed. Families with children, young adults, and people from lower socioeconomic backgrounds have been most impacted. Significant negative impacts on mental health and stress and a deterioration in protective resiliency factors were found. CONCLUSION: These population health surveys consisting of two large cross-sectional samples provided valuable insight into the impacts and experiences of British Columbians early in the pandemic and one year later. Timely, actionable data informed several high-priority public health areas during BC's response to the COVID-19 pandemic.

RéSUMé: OBJECTIFS: Décrire la méthode et les principaux constats des enquêtes SPEAK de la Colombie-Britannique sur la COVID-19, élaborées pour comprendre l'expérience des Britanno-Colombiens durant la pandémie, ainsi que leurs connaissances de la pandémie et les effets qu'elle a eus sur eux. MéTHODE: Deux enquêtes en ligne transversales sur la santé de la population ont été menées dans toute la province à un an d'intervalle (en mai 2020 et en avril-mai 2021). Les questions, qui provenaient de sources validées ancrées dans les déterminants sociaux de la santé, ont servi à évaluer le dépistage et la prévention de la COVID-19; la santé mentale et physique; les facteurs de risque et de protection; et les effets sociaux, économiques et sur les soins de santé ressentis durant la pandémie. Un échantillonnage contingentaire non probabiliste par lieu géographique a été appliqué pour recruter un échantillon représentatif de personnes de 18 ans et plus. Le recrutement a inclus une prise de contact stratégique et un suivi longitudinal auprès d'un sous-groupe de répondants entre les cycles un et deux. Après la collecte, les données ont été pondérées selon l'âge, le sexe, le niveau d'instruction, l'ethnicité et le lieu géographique à l'aide des données du Recensement. RéSULTATS: Les participants étaient 394 382 Britanno-Colombiens au cours du premier cycle de l'enquête et 188 561 au deuxième cycle, dont un sous-groupe longitudinal de 141 728 personnes. Selon les principaux constats, la répartition des effets sociétaux, tant au début de la pandémie qu'un an plus tard, a été inéquitable. Les familles avec enfants, les jeunes adultes et les personnes de statut socioéconomique plus faible ont été les plus touchés. D'importants effets nuisibles sur la santé mentale et le stress ont été constatés, ainsi qu'une détérioration des facteurs de résilience protecteurs. CONCLUSION: Ces enquêtes sur la santé de la population comprenant deux grands échantillons transversaux ont jeté un éclairage précieux sur les effets subis et les expériences vécues par les Britanno-Colombiens au début de la pandémie et un an plus tard. Ces données opportunes et exploitables ont éclairé plusieurs domaines hautement prioritaires de la santé publique durant la riposte de la Colombie-Britannique à la pandémie de COVID-19.

The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis.

Cardiac fibrosis often has adverse cardiovascular effects, including heart failure, sudden death, and malignant arrhythmias. However, there is no targeted therapy for cardiac fibrosis. Inflammation is known to play a crucial role in the disorder, and the NLR pyrin domain-containing-3 (NLRP3) inflammasome is closely associated with innate immunity. Therefore, further understanding the pathophysiological role of the inflammasome in cardiac fibrosis may provide novel strategies for the prevention and treatment of the disorder. The aim of this review was to summarize the present knowledge of NLRP3 inflammasome-related mechanisms underlying cardiac fibrosis and to suggest potential targeted therapy that could be used to treat the condition.

Cardio-Oncology: A Myriad of Relationships Between Cardiovascular Disease and Cancer.

Cardiovascular disease (CVD) and cancer are the leading causes of death worldwide. With an increasing number of the elderly population, and early cancer screening and treatment, the number of cancers cases are rising, while the mortality rate is decreasing. However, the number of cancer survivors is increasing yearly. With the prolonged life span of cancer patients, the adverse effects of anti-tumor therapy, especially CVD, have gained enormous attention. The incidence of cardiovascular events such as cardiac injury or cardiovascular toxicity is higher than malignant tumors' recurrence rate. Numerous clinical studies have also shifted their focus from the study of a single disease to the interdisciplinary study of oncology and cardiology. Previous studies have confirmed that anti-tumor therapy can cause CVD. Additionally, the treatment of CVD is also related to the tumors incidence. It is well established that the increased incidence of CVD in cancer patients is probably due to an unmodified unhealthy lifestyle among cancer survivors or cardiotoxicity caused by anti-cancer therapy. Nevertheless, some patients with CVD have a relatively increased cancer risk because CVD and malignant tumors are highly overlapping risk factors, including gender, age, hypertension, diabetes, hyperlipidemia, inflammation, and obesity. With advancements in the diagnosis and treatment, many patients simultaneously suffer from CVD and cancer, and most of them have a poor prognosis. Therefore, clinicians should understand the relationship between CVD and tumors, effectively identify the primary and secondary prevention for these diseases, and follow proper treatment methods.

The Role of Apelin-APJ System in Diabetes and Obesity.

Nowadays, diabetes and obesity are two main health-threatening metabolic disorders in the world, which increase the risk for many chronic diseases. Apelin, a peptide hormone, exerts its effect by binding with angiotensin II protein J receptor (APJ) and is considered to be linked with diabetes and obesity. Apelin and its receptor are widely present in the body and are involved in many physiological processes, such as glucose and lipid metabolism, homeostasis, endocrine response to stress, and angiogenesis. In this review, we summarize the literatures on the role of the Apelin-APJ system in diabetes and obesity for a better understanding of the mechanism and function of apelin and its receptor in the pathophysiology of diseases that may contribute to the development of new therapies.

Chronic disease and where you live: Built and natural environment relationships with physical activity, obesity, and diabetes.

BACKGROUND: Diabetes is among the most prevalent non-communicable diseases causing significant morbidity and mortality globally. The aetiology and disease development of diabetes are influenced by genetic, lifestyle, and environmental factors. Due to an increasing number of cases each year, it is imperative to improve the understanding of modifiable environmental risk and protective factors. In this study we aimed to analyse associations between built and natural environment features and diabetes prevalence; and two major risk factors: physical activity and obesity and their mediation effects. METHODS: We analysed relationships between walkability and park availability with physical activity, obesity, and diabetes, using self-reported data from a large cross-sectional survey in British Columbia, Canada (n = 22,418). We validated results with an independent cohort (n = 11,972) in a subset of the analyses. The outcome measures included walking, moderate to vigorous physical activity (MVPA), body mass index (BMI), and diabetes. Built and natural environment features within a 1 km road network buffer around residential postal code centroids were assessed using validated indicators of walkability and park availability. We used general linear multivariable models (GLM) to examine the direct relationship between environmental features, physical activity, obesity, and diabetes respectively. Path models were developed to analyse mediation effects of physical activity and obesity on the association between environmental indicators and diabetes. The relative contribution of direct versus indirect effects was assessed. All models were adjusted for age, gender, income. ethnicity, years lived in neighbourhood and regional accessibility. RESULTS: Walkable neighbourhoods and areas with greater park availability were associated with lower rates of diabetes. There was a direct association of walkability and park availability on physical activity (highest vs. lowest quintile OR = 1.15; 95% CI: 1.00, 1.33 and OR = 1.28, 95% CI: 1.13, 1.45 respectively), obesity (highest vs. lowest quintile OR = 0.58, 95% CI: 0.49, 0.70 and OR = 0.57, 95% CI: 0.48, 0.68 respectively) and diabetes (highest vs. lowest quintile OR = 0.62, 95% CI: 0.45, 0.85, and OR = 0.63, 95% CI: 0.47, 0.84 respectively). Results were similar in the independent cohort. The associations between diabetes and walkability and park availability respectively were partly mediated by obesity (41% of total association for walkability and 53% of total association for park availability). The mediating effect of physical activity was negligible. CONCLUSION: Results support investments in walkability through active transportation and transit infrastructure. Changes in zoning and subdivision regulations governing land use actions are required to enable compact mixed-use environments with access to parks and high quality transit service. Future studies including cost-benefit analyses of health-related economic impacts of such investments can contribute to evidence-based decisions for healthier cities.

Community design and hypertension: Walkability and park access relationships with cardiovascular health.

BACKGROUND: There is an increased literature focusing on the role of the built and natural environments in preventing hypertension. However, very few studies have quantitively analyzed specific pathways through which urban form affects blood pressure levels. OBJECTIVES: To examine how features of the built and natural environments relate to hypertension and the mediating role of transportation and leisure walking and body mass index in this relationship. METHODS: We examined the association between neighbourhood walkability and park availability with hypertension through generalized linear models in two independent population cohorts. One Cohort was 22,418 adults (My Health My Community) and the other cohort was 11,972 adults (BC Generations Project). We employed a path analysis modelling approach to explore the presence and significance of mediating factors that may contribute to any association between walkability or park availability and hypertension. This study intentionally employed walkability measures enforced through municipal zoning and subdivision regulations legally underpinned by health, safety, and welfare. All models were adjusted for socioeconomic and other characteristics where data were available. RESULTS: Our analysis of two population-based Canadian cohorts consistently found that higher levels of walkability and park accessibility were both associated with significantly lower odds of self-reported hypertension, especially for lower income individuals. Mediation analysis showed that obesity accounted for 50% and 52.9% of the total effect of walkability and park accessibility on hypertension, respectively. DISCUSSION: We suggest an integrated population health approach that considers multimorbidity as a result of exposure to car-dependent areas and the lack of green spaces. Longitudinal research is needed to document causal effects of built and natural environments on hypertension.

The digestive system involvement of antiphospholipid syndrome: pathophysiology, clinical characteristics, and treatment strategies.

Antiphospholipid syndrome (APS) is an autoimmune disease mainly characterised by vascular thrombosis and pregnancy morbidity. APS has broad spectrum of clinical manifestations. The digestive system involvement of antiphospholipid syndrome is a critical but under-recognised condition. Digestive system involvement may be the result of direct (autoimmune-mediated) or indirect (thrombotic) mechanisms. Liver is the most commonly involved organ, followed by intestines, oesophagus, stomach, pancreas and spleen. This review describes possible digestive system manifestations in APS patients, and illustrates the epidemiology and possible pathophysiology of APS. The role of different treatment strategies in the management of digestive system manifestations of APS were also discussed.Key messagesAntiphospholipid syndrome is a multi-organ, multi-system disease and its clinical manifestation spectrum is gradually expanding. Since the first diagnosis of APS, the clinical manifestations of digestive system have been reported successively. This narrative review describes the major digestive system manifestations of APS and illustrates the epidemiology, pathophysiology and the role of therapeutic strategies of these patients.

Ventricular fibrillation storm after revascularization of chronic total occlusion of the left anterior descending artery: is this reperfusion arrhythmia?

Electrical storm is a life-threatening emergency condition defined as three or more episodes of ventricular tachycardia or ventricular fibrillation (VF) within 24 hours requiring anti-tachycardia therapy, electrical cardioversion, or defibrillation. However, studies of the incidence of electrical storm after chronic total occlusion-percutaneous coronary intervention (CTO-PCI) are limited,7 and post-procedural VF after revascularization of CTO has not been described. The purpose of this article was to present a case of post-operative VF electrical storm after revascularization of CTO of the left anterior descending (LAD) artery to determine whether the electrical storm was caused by reperfusion arrhythmia or compromise of either branch vessels or the collateral circulation during intervention.

Congenital absence of the right coronary artery with acute myocardial infarction: report of two cases and review of the literature.

Congenital absence of the right coronary artery (RCA) is a rare coronary anomaly. Few cases of this condition have been reported. Congenital absence of the RCA is considered as a benign anomaly. However, in certain cases, these patients may develop life-threatening clinical complications that include acute myocardial infarction, stroke, or sudden death. We report two patients who were diagnosed with congenital absence of the RCA and presented with acute myocardial infarction. We discuss our experience in diagnosis and treatment of this disease. Congenital absence of the RCA with acute myocardial infarction is an uncommon clinical emergency. Therefore, early detection, correct diagnosis, and appropriate treatment are important.

Cardiac biomarkers of heart failure in chronic kidney disease.

Heart failure remains a continuing threat to patients with chronic kidney disease (CKD). Although various heart failure biomarkers have been applied for early detection, diagnosis and prognosis in CKD, these are easily affected by renal insufficiency thus limiting use in these patients. In this review, the major four groups of heart failure biomarkers are explored. These include those associated with: myocardial stretch, ie, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP); myocyte injury, ie, high-sensitivity troponin T (hsTnT), heart-type fatty acid-binding protein (H-FABP); fibrosis, matrix remodelling and inflammation, ie, soluble growth stimulating gene 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15); and renal function, ie, neutrophil gelatinase-associated lipocalin (NGAL) kidney injury molecule-1 (KIM-1), cystatin C (CysC), urinary sodium and urinary albumin. This review highlights classic heart failure biomarkers with critical values adjusted to glomerular filtration rate, summarizes research progress of new heart failure biomarkers and future research directions. Because diagnostic and prognostic usefulness of a single time point biomarker is limited, biomarkers should be combined and monitored at multiple times for optimal clinical impact.

Is CD47 a potentially promising therapeutic target in cardiovascular diseases? - Role of CD47 in cardiovascular diseases.

CD47 (cluster of differentiation 47) is a ubiquitously expressed transmembrane protein that belongs to the immunoglobulin superfamily. CD47 is both a receptor for the matricellular protein thrombospondin-1 (TSP-1) and a ligand for signal-regulatory protein alpha (SIRPα). Suppression of CD47 activity enhances angiogenesis and blood flow, restores phagocytosis by macrophages, improves ischemic tissue survival, attenuates ischemia reperfusion injury, and reverses atherosclerotic plaque formation. In conclusion, these observations suggest a pathogenic role of CD47 in the development of cardiovascular diseases (CVDs) and indicate that CD47 might be a potentially promising molecular target for treating CVDs. Herein, we highlight the role of CD47 in the CVD pathogenesis and discuss the potential clinical application by targeting CD47 for treating CVDs.

Pericardial malignant solitary fibrous tumour with right atrial invasion - a case report and literature review.

Solitary fibrous tumours are unusual neoplasms that develop from mesenchymal cells, usually originating from the pleura. A pericardial solitary fibrous tumour is an extremely rare occurrence. We report a 64-year-old woman who presented to the hospital with chief complaints of dyspnoea and abdominal distension. Echocardiography and enhanced computed tomography revealed an intrapericardial tumour with local invasion to the right atrium. Histopathological examination of a biopsy specimen showed a patternless distribution of spindle-shaped cells in a collagen stroma, with a high mitosis rate. Immunohistochemistry was positive for vimentin, CD34, and Bcl-2. The final diagnosis was a pericardial malignant solitary fibrous tumour with right atrial invasion. Surgical resection of the tumour was not performed because of its invasion into the myocardium. We systematically reviewed the literature on cardiac solitary fibrous tumours up to 2019.

Curcuminoids: Implication for inflammation and oxidative stress in cardiovascular diseases.

It has been extensively verified that inflammation and oxidative stress play important roles in the pathogenesis of cardiovascular diseases (CVDs). Curcuminoids, from the plant Curcuma longa, have three major active ingredients, which include curcumin (curcumin I), demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have been used in traditional medicine for CVDs' management and other comorbidities for centuries. Numerous studies had delineated their anti-inflammatory, antioxidative, and other medicinally relevant properties. Animal experiments and clinical trials have also demonstrated that turmeric and curcuminoids can effectively reduce atherosclerosis, cardiac hypertrophy, hypertension, ischemia/reperfusion injury, and diabetic cardiovascular complications. In this review, we introduce and summarize curcuminoids' molecular and biological significance, while focusing on their mechanistic anti-inflammatory/antioxidative involvements in CVDs and preventive effects against CVDs, and, finally, discuss relevant clinical applications.

Idiopathic hypereosinophilic syndrome with pulmonary hypertension.

Hypereosinophilic syndrome is a myeloproliferative disorder characterized by persistent eosinophilia with involvement of multiple organs. The occurrence of severe pulmonary hypertension (PH) in the setting of hypereosinophilic syndrome is very uncommon. A 43-year-old man with documented idiopathic hypereosinophlic syndrome presented to the hospital with symptoms of paroxysmal chest discomfort and progressive exertional dyspnea. Physical examination showed distended jugular veins, cyanosed lips, increased P2 sound, and moderate pitting edema of the lower extremities. Echocardiography revealed enlarged right atrium, enlarged right ventricle, increased pulmonary artery systolic pressure, and decreased right ventricular systolic function. Venous ultrasound of the lower extremities, computed tomography pulmonary angiography, and right heart catheterization (RHC) were negative for thrombus. The pulmonary artery systolic pressure was found severely increased during the RHC. Treatment included prednisolone, ambrisentan, diuretics, and digoxin. The involvement of the pulmonary artery in patients with idiopathic hypereosinophilic syndrome is an uncommon finding. The patient presents with clinical manifestations of right ventricular systolic dysfunction resulted from severely increased PH.

Cardioprotective effects of the novel curcumin analogue C66 in diabetic mice is dependent on JNK2 inactivation.

AIM: Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes-induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66-mediated cardioprotection. METHODS: An experimental diabetic model was established using JNK2-/- and wild-type (WT) mice. C66 (5 mg/kg) was administered orally every other day for 3 months. Body weight, plasma glucose levels, cardiac function, and structure were measured. Masson trichrome and TUNEL staining were used to assess myocardial fibrosis and apoptosis, respectively. mRNA and protein levels of inflammation, fibrosis, oxidative stress, and apoptosis molecules were measured by quantitative PCR and Western blot, respectively. RESULTS: Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2-/- diabetic mice compared to JNK2-/- control mice, and C66 treatment did not further affect these parameters in JNK2-/- diabetic mice. CONCLUSIONS: Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.