Low Concentration of Lipoprotein(a) is an Independent Predictor of Incident Type 2 Diabetes.

The aim of the study was to assess the association between lipoprotein(a) [Lp(a)] concentration and incident type 2 diabetes. A meta-analysis of qualified studies on the relationship of low levels of Lp(a) concentration with incident type 2 diabetes was conducted. PubMed and Cochrane libraries were searched for randomized controlled trials containing data on events. Seven randomized trials with 227178 subjects were included in this analysis. We found an inverse association of the levels of Lp(a) concentration with risk of type 2 diabetes with approximately 37% lower relative risk in the group with the highest concentration compared with group with the lowest concentration. The current available evidence from prospective studies suggests that there is an inverse association between the levels of Lp(a) concentration and risk of type 2 diabetes, with a higher risk of type 2 diabetes at low levels of Lp(a) concentration. Therefore, we believe that the low levels of Lp(a) concentration is an independent predictor of incident type 2 diabetes.

Two cerebral infarctions caused by thrombus and myxomatous embolus in a patient with cardiac myxoma: A case report.

An increasing number of cases of cerebral embolism caused by cardiac myxoma have been reported. However, cerebral infarction caused by different types of emboli obstructing different vascular regions within a short period of time has not been reported. This is the first report to histologically confirm cerebral infarctions independently caused by thrombus and myxomatous embolus in a patient with cardiac myxoma within a period of 23 days. The first cerebral infarction was due to embolization of thrombus to the right middle cerebral artery, whereas the second was due to embolization of tissue from a mucinous tumor to the left middle cerebral artery. Both cerebral infarctions underwent mechanical thrombectomy, but unfortunately, we ultimately failed to save the patient's life. Therefore, further attention should be paid to the surgical resection and treatment of cardiac myxoma.

Fullerene [60] encapsulated water-soluble supramolecular cage for prevention of oxidative stress-induced myocardial injury.

A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C60 molecule inside of the cavity and significantly improve the water-solubility of the C60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C60 and verifies the important role of C60 in preventing oxidative stress-related cardiovascular disease injury.

MRAs may have lost their cornerstone position for heart failure treatment in the age of SGLT-2 inhibitors: A meta-analysis of randomized controlled trials.

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone drug class for heart failure therapy. Several clinical studies have demonstrated its role in heart failure therapy. However, due to the recommendation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors for the treatment of heart failure, there is a lack of sufficient evidence regarding whether MRAs can continue to play a cornerstone role in heart failure treatment. A meta-analysis was performed on subgroups of the DAPA-HF and EMPEROR-Reduced trials. Using trial-level data, we performed a meta-analysis to assess the effects of SGLT-2 inhibitors and MRAs on various clinical endpoints of heart failure. The incidence of cardiovascular-related death or heart failure hospitalization was the primary outcome. In addition, we assessed cardiovascular death, all-cause death, heart failure hospitalization, renal outcomes, and hyperkalemia. This study has already been registered with PROSPERO, CRD42022385023. Compared with SGLT-2 inhibitor monotherapy, combined treatment did not demonstrate more significant advantages in terms of heart failure or cardiovascular death (RR = 1.00; 95% CI: 0.78-1.28), cardiovascular death (RR = 0.96; 95% CI: 0.61-1.52), heart failure hospitalization (RR = 0.92; 95% CI: 0.79-1.07), all-cause death (RR = 1.00; 95% CI: 0.63-1.59) and composite kidney endpoint (RR = 0.85; 95% CI: 0.49-1.46). Moreover, in comparison to SGLT-2 inhibitors, combined therapy increased the risk of moderate-severe hyperkalemia (blood potassium > 6.0 mmol/l) (RR = 4.13; 95% CI: 2.23-7.65). In patients with HFrEF who have started MRAs treatment, the addition of an SGLT-2 inhibitor provides significant clinical benefit. However, the addition of MRAs to SGLT-2 inhibitors to treat heart failure is not essential.

Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway.

BACKGROUND AND AIMS: As a member of mitochondrial sirtuins, Sirt4 plays a vital role in cellular metabolism and intracellular signal transduction; however, its effect on atherosclerosis is unclear. This study aimed to explore the effect of Sirt4 on atherosclerosis and its underlying mechanism. METHODS: In vivo, Apoe-/- and Apoe-/-/Sirt4-/- mice were fed a high-fat diet to induce atherosclerosis. In vitro, peritoneal macrophages from two mouse types were extracted and treated with oxidized low-density lipoprotein to establish a cell model, THP-1 cells were used to observe the effect of Sirt4 on the adhesion ability of monocytes. The growth and composition of aortic plaques in two mouse types were analyzed by H&E staining, Oil Red O staining, Dil oxidized low-density lipoprotein, immunohistochemistry, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Transcriptome analysis and Western blotting were performed to explore the specific mechanism. RESULTS: Sirt4 deficiency aggravated atherosclerosis in mice. In vivo, aortic plaque size, lipid content, and expression of related inflammatory factors in Apoe-/-/Sirt4-/- mice were higher than those in the control group, whereas the content of collagen Ⅰ and smooth muscle actin-α was significantly lower. Sirt4-deficient macrophages exhibited stronger lipid phagocytosis in vitro, and the adhesion ability of monocytes increased when Sirt4 expression decreased. Transcriptome analysis showed that the expression of CXCL2 and CXCL3 in Sirt4-deficient peritoneal macrophages increased significantly, which may play a role by activating the NF-κB pathway. In further analysis, the results in vitro and in vivo showed that the expression of VCAM-1 and pro-inflammatory factors, such as IL-6, TNF-α and IL-1ß, increased, whereas the expression of anti-inflammatory factor IL-37 decreased in Sirt4-deficient peritoneal macrophages and tissues. After blocking the effect with NK-κB inhibitor BAY11-7082, the inflammatory reaction in sirt4 deficient macrophages was also significantly decreased. CONCLUSIONS: This study demonstrates that Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway, suggesting that Sirt4 may exhibit a protective effect in atherosclerosis, which provides a new strategy for clinical prevention and treatment of atherosclerosis.