Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic disorders that significantly elevate the risk of cardiovascular disease, making it a pressing public health concern worldwide. Among the key features of MetS, dyslipidemia—characterized by altered levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)—plays a crucial role in the disorder’s progression. This review aims to elucidate the intricate interplay between HDL-C and TG within the context of lipid metabolism and cardiovascular health, while also addressing the detrimental impact of various cardiovascular risk factors and associated comorbidities. The dynamics of HDL-C and TG are explored, highlighting their reciprocal relationship and respective contributions to the pathophysiology of MetS. Elevated levels of TGs are consistently associated with reduced concentrations of HDL-C, resulting in a lipid profile that promotes the development of vascular disease. Specifically, as TG levels rise, the protective cardiovascular effects of HDL-C are diminished, leading to the increased accumulation of pro-atherogenic TG-rich lipoproteins and low-density lipoprotein particles within the vascular wall, contributing to the progression of atheromas, which can ultimately result in significant ischemic cardiovascular events. Ultimately, this paper underscores the significance of HDL and TG as essential targets for therapeutic intervention, emphasizing their potential in effectively managing MetS and reducing cardiovascular risk.

Myocardial infarction (MI) sets off a complex inflammatory cascade that is crucial for effective cardiac healing and scar formation. Yet, if this response becomes excessive or uncontrolled, it can lead to cardiovascular complications. This review aims to provide a comprehensive overview of the tightly regulated local inflammatory response triggered in the early post-MI phase involving cardiomyocytes, (myo)fibroblasts, endothelial cells, and infiltrating immune cells. Next, we explore how the bone marrow and extramedullary hematopoiesis (such as in the spleen) contribute to sustaining immune cell supply at a cardiac level. Lastly, we discuss recent findings on how metabolic cardiovascular risk factors, including hypercholesterolemia, hypertriglyceridemia, diabetes, and hypertension, disrupt this immunological response and explore the potential modulatory effects of lifestyle habits and pharmacological interventions. Understanding how different metabolic risk factors influence the inflammatory response triggered by MI and unraveling the underlying molecular and cellular mechanisms may pave the way for developing personalized therapeutic approaches based on the patient’s metabolic profile. Similarly, delving deeper into the impact of lifestyle modifications on the inflammatory response post-MI is crucial. These insights may enable the adoption of more effective strategies to manage post-MI inflammation and improve cardiovascular health outcomes in a holistic manner.

Patients with diabetes are at an increased risk of diabetic cardiomyopathy (DCM) and acute myocardial infarction (AMI). Protecting the heart against AMI is more challenging in DCM than in nondiabetic hearts. We investigated whether intravenous (i.v.) atorvastatin administration during AMI exerts cardioprotection in DCM as seen in nondiabetic hearts. Sprague-Dawley rats were divided into streptozotocin-induced DCM and normoglycemic control groups. Our model of DCM rats exhibited interstitial fibrosis and cardiac dysfunction at 5 weeks. At this time point, all animals underwent AMI induction (coronary ligation for 45 min), receiving i.v. atorvastatin or vehicle during ischemia. Animals were reperfused and sacrificed 24 h later for myocardial infarct size analysis and cardiac tissue sampling. Echocardiography was performed. DCM vehicle rats had larger infarcts than normoglycemic vehicle-treated animals at a comparable area-at-risk. Intravenous atorvastatin reduced infarct size and preserved systolic function in both groups. Compared with vehicle animals, i.v. atorvastatin inhibited RhoA membrane translocation, induced AMPK phosphorylation, prevented apoptosis execution, and improved cardiac remodelling in the infarcted heart of both groups, whereas innate immune cell infiltration was further reduced in i.v. atorvastatin-treated DCM animals. The proven cardioprotective effectiveness of this i.v. statin formulation in the presence of DCM warrants its further development into a clinically therapeutic option. Article Highlights: Diabetic cardiomyopathy (DCM) significantly increases the risk of acute myocardial infarction and attenuates or abolishes the cardioprotective effects of several therapeutic approaches. Whether intravenous atorvastatin administration during ongoing acute myocardial infarction retains its cardioprotective potential in the presence of DCM was investigated. Intravenous atorvastatin during ischemia reduces infarct size and preserves cardiac function in DCM rats. The efficacy of this intravenous statin formulation in DCM supports its development as a viable therapeutic option for clinical use.

Background and Aims: The cardiovascular benefits of eicosapentaenoic acid ethyl ester (EPA-E) in MACE reduction might extend beyond its triglyceride (TG)-lowering effects. However, the mechanism behind remains unknown. This study investigated whether EPA-E exerts cardioprotection in the setting of myocardial infarction (MI). Methods: Hypertriglyceridaemia (HTG) was induced in male rats by a high-sucrose diet (>175 mg·dL−1; baseline). Hypertriglyceridaemia rats were administered for 2 weeks high-dose EPA-E supplementation (HTG + EPA-E; n = 21) or placebo (HTG; n = 27) in combination with the diet. A control diet group (CD; n = 15) was included. After 2 weeks, MI was induced by transient coronary ligation and animals were sacrificed 24 h thereafter for infarct size, molecular, histological, and -omic analyses. Echocardiography was performed. Results: HTG + EPA-E animals displayed lower circulating TG levels and better cardiac function as compared to HTG group. HTG + EPA-E animals showed smaller infarcts (P < 0.05 vs both groups), and MI-related mortality was 29% in EPA-E-treated animals (reaching levels comparable to those of the CD group), whereas it was 56% in HTG animals (P = 0.07). No correlation was observed between circulating TG levels and MI-related infarct size or mortality. Cardiac function was similarly deteriorated in all animals post-MI. Eicosapentaenoic acid ethyl ester treatment was associated with lower TG-related cardiolipotoxicity, apoptosis, fibrosis, oxidative stress, pro-inflammatory cell recruitment and less mitochondrial dysfunction in the infarcted heart. EPA-E treatment favoured a pro-resolving response and improved metabolomic and lipidomic profiles both systemically and in the infarcted heart. Conclusions: Eicosapentaenoic acid ethyl ester treatment exerts direct cardioprotective effects and ameliorates cardiac metabolic and lipidomic signatures after MI regardless of its circulating TG-lowering effects.

Aims: Acute myocardial infarction (AMI) triggers an immune response characterized by a dynamic interplay between the bone marrow (BM) and the ischaemic heart. However, the effect of metabolic alterations such as hypertriglyceridaemia (HTG) on this inter-organ communication remains unknown. In the present study, we have investigated, in a rat model of crossed-BM transplant, the impact of HTG on the BM–heart axis response to AMI under constant metabolic stress. Methods and results: Wistar rats (n = 56) were assigned to two groups: one fed a high-sucrose diet to induce HTG and the other fed a regular chow [normolipemic (NL)-animals]. After 3 weeks, all combinations of crossed-BM transplants were performed (NL-BM/NL-recipient, NL-BM/HTG-recipient, HTG-BM/NL-recipient, and HTG-BM/HTG-recipient) following total body irradiation (9.5 Gy). All animals, except for the NL-BM/NL-recipient group, continued on a high-sucrose diet for 3 weeks. Then, AMI was induced by transient coronary artery ligation, and 5 days later, animals were sacrificed. We determined infarct size and performed echocardiography, 1H-NMR spectroscopy, and multiple molecular and histological analyses. NL-BM/HTG-recipients exhibited smaller infarcts vs. the other groups and showed a resolving inflammatory response, lower lipotoxicity, higher ω3 content, increased AMPK activation and S1P-related enzymes, and reparative fibrosis in the healing scar. Although no differences were detected in left ventricular ejection fraction post-AMI among all groups, NL-BM/HTG-recipients exhibited improved systolic and diastolic parameters. Circulating triglyceride levels were significantly reduced in NL-BM/HTG-recipients 3 weeks post-BM transplant, whereas, conversely, they were found to be enhanced in HTG-BM/NL-recipients developing a HTG state. Furthermore, recipients of a HTG-BM showed a worsened lipid profile, liver steatosis and inflammation, higher weight gain, leptin levels and lower lipoprotein lipase, AMPK, and acetyl-CoA carboxylase activity in the visceral adipose tissue vs. NL-BM-recipient animals. Conclusion: Transplantation of healthy BM into HTG animals enhances the capacity to counteract myocardial injury post-AMI and restores metabolic disturbances, improving overall recovery.