Doxorubicin is a major culprit in chemotherapy-induced cardiotoxicity, which is the chief limiting factor in delivering optimal chemotherapy to cancer patients. Although extensive efforts have been devoted, no chemical synthesized drugs or natural compounds are available to prevent the harmful action of doxorubicin without reducing its anti-cancer efficacy. Accumulative experimental evidence has shown that polyphenols can prevent doxorubicin-induced cardiotoxicity largely due to their anti-cancer and cardio protective properties. We elaborated on the potential mechanisms associated with doxorubicin-induced cardiotoxicity and reviewed published literatures about the protective effects of polyphenols on doxorubicin-induced cardiotoxicity to provide novel strategies for the study of cardioprotective drugs.
Key words:
Doxorubicin/AE; Cardiomyopathies/CI; Phenols/PD; Review
Angiotensin II (Ang II) is reported to be involved in the development of various cardiovascular diseases by disrupting microvessel permeability, however, the underlying mechanism remains to be elucidated. The present study aimed to investigate the mechanism by which Ang II disrupts microvascular permeability. Rat endothelial cells were subjected to primary culture and identification. Cells in passages 4‑7 were then used for the following experiments. The cells were divided into control, Ang II, and Ang II + valsartan groups, and reverse transcription‑quantitative polymerase chain reaction and western blot analyses were perform to evaluate the expression of zonula occludens‑1 (ZO‑1) and vascular endothelial (VE)‑cadherin in the cells. The distribution of ZO‑1 protein was also detected using immunofluorescence assays. It was found that, compared with the control group, lower expression levels of ZO‑1 and VE‑cadherin were present in the Ang II group (P<0.01). ZO‑1 was also irregularly distributed at the periphery of the cells. In addition, the overexpression of VE‑cadherin reversed the effect of Ang II on the expression and distribution of ZO‑1 in endothelial cells. Together, these results suggested that Ang II inhibited the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin, thus destroying the tight junctions between endothelial cells, which may also be the mechanism by which Ang II is involved in the development of cardiovascular diseases.
Abstract Background: N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. Methods: DCM rat model was established and qRT-PCR, western blot and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Results : In vivo and in vitro studies showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 through increasing its mRNA stability. Conclusions: Our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.
Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08–1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01–2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64–0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96–1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98–1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37–1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46–1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34–2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38–0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.
We present a case of a coronary arteriovenous fistula between the left circumflex (LCX) and the atrium with LCX ectasia. Four months after surgical closure of the fistula, the patient experienced acute myocardial infarction caused by thrombosis in the LCX. Antiplatelet drugs were replaced with anticoagulant agents, and the patient was followed up without adverse events. (Level of Difficulty: Advanced.).
Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and to elucidate the molecular processes underlying this effect. LDLR-/- mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α-actin (α-SMA) antibodies and anti-osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α-SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high-fat-fed LDLR-/- mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.
With the spread and establishment of the Chest Pain Center in China, adhering to the idea that "time is myocardial cell and time is life", many hospitals have set up a standardized process that ensures that patients with acute myocardial infarction (AMI) who meet emergency percutaneous coronary intervention (PCI) guidelines are sent directly to the DSA room by the prehospital emergency doctor, saving the time spent on queuing, registration, payment, re-examination by the emergency doctor, and obtaining consent for surgery after arriving at the hospital. Takotsubo cardiomyopathy is an acute disease that is triggered by intense emotional or physical stress and must be promptly differentiated from AMI for its appropriate management.
This study explored the immunomodulatory effects of a prebiotic formula consisting of 2'-fucosyllactose (2'-FL), galacto-oligosaccharides (GOSs), and fructo-oligosaccharides (FOSs) (hereinafter referred to as 2FGF) in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice and its underlying mechanisms.
Abstract Background Increased Hcy level is an independent risk factor for coronary heart disease (CHD). It was proposed that yellow rice wine improves Hcy-induced EPCs dysfunction and inhibits the development of atherosclerotic plaques. In this study, we observed whether yellow rice wine and red wine improve the properties of homocysteine (Hcy)-induced endothelial progenitor cells (EPCs). Methods The bone marrow of rats was extracted to isolate EPCs from the bone marrow cell suspension using density-gradient centrifugation. The cells were inoculated on culture plates coated with human fibronectin (HFN), to induce mononuclear cell differentiation into EPCs. Samples were divided into 5 groups including a control group. Western blotting. and NO assays were used respectively to observe the generation of eNOS, p-eNOS and NO. MTT and transwell assays were conducted. Apoptosis and in vitro angiogenesis of EPCs were determined. Results Compared with the control group, the potential for proliferation, migration and in vitro angiogenesis of EPCs decreased significantly following Hcy intervention (P < 0.01).The production of eNOS, NO and p-eNOS was significantly reduced (P < 0.01). Intervention with yellow rice wine and red wine significantly improved the effect of Hcy in EPCs (P < 0.01). Further, comparison with the control group indicated that the intervention also significantly improved the proliferation, migration and angiogenesis of EPCs in vitro (P < 0.05). Compared with the Hcy group, the alcohol group did not show significant functional changes in EPCs (P > 0.05). No impact on apoptotic function of EPCs was observed (P > 0.05). Hcy significantly lowers the capacity of proliferation, migration and in vitro angiogenesis of EPCs and reduces the production of eNOS, p-eNOS and NO. Conclusion Our results showed Hcy significantly lowers the capacity of proliferation, migration and in vitro angiogenesis of EPCs and reduces the production of eNOS, p-eNOS and NO,which indicates that yellow rice wine and red wine in small doses improve the functions of EPCs.
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