Hepatocellular carcinoma (HCC) patients suffer varying degrees of heart dysfunction after tyrosine kinase inhibitor (TKI) treatment. Interestingly, HCC patients often have higher levels of pentraxin 3 (PTX3), and PTX3 inhibition was found to improve left ventricular dysfunction in animal models. We sought to assess the therapeutic potential of PTX3 inhibition on TKI-associated cardiotoxicity. We used a human embryonic stem cell line, RUES2, to generate cardiomyocyte cultures (RUES2-CM) for functional testing. We also assessed heart function and PTX3 expression levels in 16 HCC patients who received TKI treatment, 3 HCC patients who did not receive TKIs, and 7 healthy volunteers. Significantly higher PTX3 expression was noted in HCC patients with TKI treatment versus those without, and 38% of male and 33% of female patients had QTc prolongation after TKI treatment. Treatment of cardiomyocyte cultures with sorafenib also increased PTX3 expression and induced cytoskeletal remodelling, contraction reduction, sodium current inhibition, and mitochondrial respiratory dysfunction. PTX3 colocalised with CD44 in cardiomyocytes, and cardiomyocyte contraction, mitochondrial respiratory function, and regular cytoskeletal and apoptotic protein expression were restored with PTX3 inhibition. CD44 knockdown confirmed PTX3/CD44 signalling. These results suggest a possible mechanism in which sorafenib treatment increases PTX3 expression, thereby resulting in reduced extracellular signal-regulated kinase (ERK) 1/2 expression that affects cardiomyocyte contraction, while also activating c-Jun N-terminal kinase (JNK) downstream pathways to disrupt mitochondrial respiration and trigger apoptosis. TKI-induced cardiotoxicity may be partly mediated by the upregulation of PTX3, and thus PTX3 inhibition has potential as a therapeutic strategy.

Glycosylation is an important step in post-translational protein modification. Altered glycosylation results in an abnormality that causes diseases such as malignancy and cardiovascular diseases. Recent emerging evidence highlights the importance of glycosylation in vascular calcification. Two major types of glycosylation, N-glycosylation and O-glycosylation, are involved in vascular calcification. Other glycosylation mechanisms, which polymerize the glycosaminoglycan (GAG) chain onto protein, resulting in proteoglycan (PG), also have an impact on vascular calcification. This paper discusses the role of glycosylation in vascular calcification.

Diabetes, dyslipidemia, obesity, and cardiac dysfunction are the hallmarks of the cardiometabolic syndrome. Pathogens include hypercoagulability, inflammation, endothelial dysfunction, and oxidative stress. Increased white fat, nonalcoholic fatty liver disease, diabetes, and cardiovascular disease are caused by obesity. Depression increases the risk of future obesity, a surprising link between obesity and neuropathology. High glucose levels, abnormal lipids, and metabolic syndrome are the root causes of CVD associated with diabetes. Diets high in fat induce insulin resistance and liver fat. Inflammation, diminished insulin signaling, and ectopic lipid accumulation are the causes of ectopic lipid accumulation. Polyunsaturated fatty acids with eicosapentaenoic acid and docohexasonoic acid inhibit the synthesis of triglycerides and increase their clearance. Omega-3 regulates the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammation. However, anxiety and depression can cause cardiovascular disease. It has been shown that PUFAs found in fish oil can improve glucose and lipid metabolism, cardiac membrane composition, and inflammation in the body. By repairing the dysregulation of metabolic syndrome, fish oil is a potential therapeutic target for cardiovascular diseases.

Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have been widely reported. Tyrosine kinase is involved in many regulatory processes in a cell, and it is involved in cancer formation. Recent evidence suggests the role of tyrosine kinase in cardiovascular calcification, specifically, the calcification of heart vessels and valves. Herein, we summarized the accumulating evidence of the crucial role of receptor tyrosine kinase (RTK) in cardiovascular calcification and provided the potential clinical implication of TKIs-related ectopic calcification. We found that RTKs, depending on the ligand and tissue, can induce or suppress cardiovascular calcification. Therefore, RTKs may have varying effects on ectopic calcification. Additionally, in the context of cardiovascular calcification, TKIs do not always relate to an unfavored outcome—they might offer benefits in some cases.

Numerous studies have investigated in-stent restenosis (ISR) predictors in first-generation drug-eluting stents (DESs), but only a few have investigated second-generation DESs. We aimed to investigate the ISR predictors following a successful DES implantation in coronary artery disease (CAD) patients. A systematic review and meta-analysis study was conducted. Diabetes mellitus (DM) (OR 1.47; 95% CI 1.19 to 1.83; p < 0.01), family history of CAD (OR 1.26; 95% CI 1.03 to 1.55; p 0.03), and smoking (OR 1.23; 95% CI 1.02 to 1.48; p 0.03) were the strong predictors for the DES-ISR. The DES-ISR was more common in DESs with smaller stent diameter (MD −0.12; 95% CI −0.16 to −0.08; p < 0.01) and longer stent length (MD 2.24; 95% CI 1.36 to 3.13; p < 0.01). Angiography characteristics, including multi-vessel disease (MVD) (OR 1.45; 95% CI 1.07 to 1.97; p 0.02), type B2/C lesions (OR 1.56; 95% CI 1.06 to 2.30; p 0.02), and type C lesion (OR 1.33; 95% CI 1.09 to 1.62; p < 0.01), were also associated with DES-ISR. We confirmed that DM, family history of CAD, smoking, MVD, smaller stent diameter, longer stent length, and type B2 or C lesions were proven to be ISR predictors following DES implantation.