Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid–TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5–DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.

COVID-19 is the current public health threat all over the world. Unfortunately, there is no specific prevention and treatment strategy for this disease. We aim to explore the potential role of angiotensin-converting enzyme 2 (ACE2) in this regard through this literature review. As a crucial enzyme of renin-angiotensin-aldosterone system (RAAS), ACE2 not only mediates the virus entry but also affects the pathophysiological process of virus-induced acute lung injury (ALI), as well as other organs’ damage. As interaction of COVID-19 virus spike and ACE2 is essential for virus infection, COVID-19-specific vaccine based on spike protein, small molecule compound interrupting their interaction, human monoclonal antibody based on receptor-binding domain, and recombinant human ACE2 protein (rhuACE2) have aroused the interests of researchers. Meanwhile, ACE2 could catalyze angiotensin II (Ang II) to form angiotensin 1-7 (Ang 1-7), thus alleviates the harmful effect of Ang II and amplifies the protection effect of Ang1-7. ACE inhibitor and angiotensin II receptor blocker (ARB) have been shown to increase the level of expression of ACE2 and could be potential strategies in protecting lungs, heart, and kidneys. ACE2 plays a very important role in the pathogenesis and pathophysiology of COVID-19 infection. Strategies targeting ACE2 and its ligand, COVID-19 virus spike protein, may provide novel method in the prevention and management of novel coronavirus pneumonia.

Background: Atherogenic index of plasma (AIP) has been reported as a critical predictor on the risks and clinical outcomes of cardiovascular diseases (CVDs), and we aimed to explore the potential predictive value of cumulative AIP on major adverse cardiac events (MACE), stroke, myocardial infarction (MI) and cardiovascular mortality. Methods: A large-scale community-based prospective cohort was established from December 2011 to April 2012 and followed up in May to July 2014. The endpoint outcomes were obtained before December 31, 2021. AIP was calculated as the logarithmically transformed ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-c) and cumulative AIP was the average value of AIP in 2012 and 2014. Results: An overall of 3820 participants (36.1% male) with mean (SD) age of 59.1 (8.7) years, were enrolled. Within a median follow-up of 7.5 years, a total of 371 (9.7%) participants were documented with MACE, 293 (7.7%) participants developed stroke, 68 (1.8%) suffered from MI and 65 (1.7%) experienced cardiovascular mortality. Multivariable Cox regression analysis revealed significant associations between cumulative AIP and the risk of MACE, stroke and MI. Regarding MACE, individuals with one higher unit of cumulative AIP were associated with 75% increment on the incidence of going through MACE in fully adjusted model, while categorizing participants into four groups, individuals in the highest cumulative AIP quartile were significantly associated with increased incidence of MACE (HR = 1.76, 95%CI: 1.27–2.44, p < 0.001 in fully adjusted model), stroke (HR = 1.69, 95%CI: 1.17–2.45, p = 0.005) and MI (HR = 2.82, 95%CI: 1.18–6.72, p = 0.019). But not a significant association was observed between cumulative AIP and cardiovascular mortality. In subgroup analysis, the association of cumulative AIP and the incidence of stroke was more pronounced in the elderly (HR: 0.89 vs. 2.41 for the age groups < 65 years and ≥ 65 years, p for interaction = 0.018). Conclusions: A higher cumulative AIP was significantly associated with an increased risk of MACE, stroke and MI independent of traditional cardiovascular risk factors in a community-based population, and the association of cumulative AIP and stroke was particularly pronounced in the elderly population.

Previous studies established a possible link among hyperhomocysteinemia (HHcy), dyslipidemia, and atherosclerosis. However, there was limited epidemic data concerning the relation between HHcy and lipid profiles, especially in community-based Chinese populations. This study aim to investigate the association of plasma homocysteine (Hcy) level with lipid profiles in a Chinese community-based population without lipid-lowering treatment. A total of 4660 Chinese subjects from a cohort of the Shijingshan district in Beijing were included in the analysis. Plasma total Hcy, serum lipid files including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) as well as relevant metabolic risk factors were measured. Multivariate regression models adjusting for age, gender, smoking, drinking, physical activity, vitamin B supplement, body mass index, fasting blood glucose level, serum creatinine, systolic and diastolic blood pressure were used to evaluate associations of Hcy and lipid profiles. Subjects were 56.75 ± 8.91 years old, and 38.15% were male. Median (IQR) Hcy was 11.98 (10.00–14.93) μmol/L, and 24.4% had HHcy (defined as Hcy ≥ 15 μmol/L). Mean (SD) baseline TC was 5.34 ± 0.98 mmol/L, LDL-C was 3.27 ± 0.81 mmol/L, and HDL-C was 1.43 ± 0.38 mmol/L. Median (IQR) of TG was 1.28 (0.91–1.85) mmol/L. In multivariable linear-regression analyses, lnHcy (ln transformation for Hcy) level was positively associated with lnTG (adjusted β = 0.075, SE = 0.021, P = 0.001). Using Hcy < 15 μmol/L as a reference, HHcy was independently associated with both lnTG (adjusted β = 0.056, SE = 0.020, P = 0.004) and lnHDL (adjusted β = −0.018, SE = 0.009, P = 0.038). In multivariable logistic-regression analyses, HHcy was associated with increasing risk of low HDL-C (HDL-C < 1.04 mmol/L; adjusted odds ratio [OR] =1.406, 95% confidence interval [CI]: 1.143 – 1.728, P = 0.001) and hypertriglyceridemia (TG ≥ 1.7 mmol/L; adjusted OR = 1.293, 95% CI: 1.096–1.524, P = 0.002) after adjusting the confounders. However, there were no significant associations between Hcy and TC or LDL-C. The present study showed that HHcy was independently associated with hypertriglyceridemia and low levels of HDL-C, which provides evidence that Hcy levels might affect HDL-C and TG metabolism.

Folate is a crucial nutrient that supports physiological functions. Low folate levels is a risk factor for several diseases, including cardiovascular diseases and neural tube defects. The most used folate supplement is folic acid, a synthetic oxidative form, and folic acid grain fortification is a success story of public health. However, the metabolic conversion of folic acid to bioactive tetrahydrofolate requires several enzymes and cofactors. Therefore, these factors influence its bioavailability and efficacy. In contrast, 5-methyltetrahydrofolate is used directly and participates in one-carbon metabolism, and the use of 5-methyltetrahydrofolate as an alternative folate supplement has increased. The metabolism of 5-methyltetrahydrofolate is primarily dependent on the transmembrane transporter, reduced folate carrier (RFC), and the RFC gene SLC19A1 variant is a functional polymorphism that affects folate status indexes. Recent studies demonstrated that the expression of RFC and cystathionine β-synthase, another enzyme required for homocysteine clearance, increases significantly by supplementation with calcitriol (vitamin D3), suggesting that calcitriol intake promotes the bioavailability of folate and has synergistic effects in homocysteine clearance. The advancements in biomedical and cohort studies and clinical trials have enhanced our understanding of the critical roles of folate and the regulation of one-carbon metabolism. We anticipate that the field of folate supplementation is poised to evolve from one size for all to personalized, precision, poly-paths (3Ps), which is a critical measure to meet individual needs, maximize health benefits, and minimize side effects.

Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin‐converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS‐CoV‐2‐induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS‐CoV‐2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS‐CoV). The high binding affinity of SARS‐CoV‐2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin‐angiotensin‐aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1–7, which exerts a beneficial effect on coronavirus‐induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS‐CoV‐2 by blocking virus entry and redressing the imbalance of RAAS in SARS‐CoV‐2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS‐CoV‐2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.