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The dynamic balance of cardiomyocytes and neurons is essential to maintain the normal physiological functions of heart and brain. If excessive cells die in tissues, serious Cardio-Cerebrovascular Diseases would occur, namely, hypertension, myocardial infarction, and ischemic stroke. The regulation of cell death plays a role in promoting or alleviating Cardio-Cerebrovascular Diseases. Ferroptosis is an iron-dependent new type of cell death that has been proved to occur in a variety of diseases. In our review, we focus on the critical role of ferroptosis and its regulatory mechanisms involved in Cardio-Cerebrovascular Diseases, and discuss the important function of ferroptosis-related inhibitors in order to propose potential implications for the prevention and treatment of Cardio-Cerebrovascular Diseases.

Cardio-Cerebrovascular Disease is a collective term for cardiovascular disease and cerebrovascular disease, being a serious threat to human health. A growing number of studies have proved that the content of inflammatory factors or mediators determines the stability of vascular plaque and the incidence of cardio-cerebrovascular event, and involves in the process of Cardio-Cerebrovascular Diseases. Interleukin-6 is a widely used cytokine that causes inflammation and oxidative stress, which would further result in cardiac and cerebral injury. The increased expression of interleukin-6 is closely related to atherosclerosis, myocardial infarction, heart failure and ischemic stroke. It is a key risk factor for these diseases by triggering inflammatory reaction and inducing other molecules release. Therefore, interleukin-6 may become a potential target for Cardio-Cerebrovascular Diseases in the future. This paper is aimed to discuss the expression changes and pathological mechanisms of interleukin-6 in Cardio-Cerebrovascular Diseases, and to provide a novel strategy for the prevention and treatment of Cardio-Cerebrovascular Diseases.

Pulmonary hypertension (PH) is a critical and dangerous disease in cardiovascular system. Pulmonary vascular remodeling is an important pathophysiological mechanism for the development of pulmonary arterial hypertension. Pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy, and enhancing secretory activity are the main causes of pulmonary vascular remodeling. Previous studies have proven that various active substances and inflammatory factors, such as interleukin 6 (IL-6), IL-8, chemotactic factor for monocyte 1, etc., are involved in pulmonary vascular remodeling in PH. However, the underlying mechanisms of these active substances to promote the PASMC proliferation remain to be elucidated. In our study, we demonstrated that PASMC senescence, as a physiopathologic mechanism, played an essential role in hypoxia-induced PASMC proliferation. In the progression of PH, senescence PASMCs could contribute to PASMC proliferation via increasing the expression of paracrine IL-6 (senescence-associated secretory phenotype). In addition, we found that activated mTOR/S6K1 pathway can promote PASMC senescence and elevate hypoxia-induced PASMC proliferation. Further study revealed that the activation of mTOR/S6K1 pathway was responsible for senescence PASMCs inducing PASMC proliferation via paracrine IL-6. Targeted inhibition of PASMC senescence could effectively suppress PASMC proliferation and relieve pulmonary vascular remodeling in PH, indicating a potential for the exploration of novel anti-PH strategies.

Backgroud: Chronic restraint stress (CRS) induces depressive-like behaviors in rodents, which involves dysregulation of hippocampal synapse formation and excessive autophagy. Adiponectin has antidepressant activity. Hydrogen sulfide (H2S) is a novel gasotransmitter. The present work was to investigate whether H2S antagonizes CRS-induced depressive-like behaviors in rats and to explore whether its potential mechanism involves ameliorated synaptic and autophagic dysregulation by upregulation of adiponectin.Methods: Depressive-like behavior was analyzed by the tail suspension test (TST), novelty suppressed feeding test (NSFT), and open field test (OFT). The structure of autophagy was observed under transmission electron microscopy. The expressions of adiponectin, beclin1, and sequestosome 1 (p62/SQSTMI) protein in hippocampus were measured by Western blot. The levels of synapsin1 (SYN1) in the hippocampus were calculated by Western blot and immunofluorescence technique.Results: The behavior experiments, including TST, NSFT, and OFT, showed that NaHS (a donor of H2S) reduced CRS-induced depressive-like behaviors. NaHS decreased the loss of hippocampal synapse as evidenced by increased the level of SYN1 in the hippocampus of CRS-exposed rats. NaHS rescued CRS-induced excessive hippocampal autophagy as evidenced by declines in the number of autophagosomes and the expression of beclin1 as well as increase in the expression of P62 in the hippocampus of CRS-exposed rats. NaHS upregulated hippocampal adiponectin expression in the CRS-exposed rats. Furthermore, neutralizing adiponectin by Anti-acrp30 reversed the protective response of NaHS to CRS-produced depressive-like behaviors as well as hippocampal synaptic disruption and excessive autophagy.Conclusion: H2S mitigates CRS-induced depressive behavior via upregulation of adiponectin, which in turn results in amelioration in hippocampal synapse formation dysfunction and excessive autophagy.