MicroRNA Involvement in Immune Activation During Heart Failure

Heart failure is one of the common end stages of cardiovascular diseases, the leading cause of death in developed countries. Molecular mechanisms underlying the development of heart failure remain elusive but there is a consistent observation of chronic immune activation and aberrant microRNA (miRNA) expression that is present in failing hearts. This review will focus on the interplay between the immune system and miRNAs as factors that play a role during the development of heart failure. Several studies have shown that heart failure patients can be characterized by a sustained innate immune activation. The role of inflammatory signaling is discussed and TLR4 signaling, IL-1β, TNFα and IL-6 expression appears to coincide with the development of heart failure. Furthermore, we describe the implication of the renin angiotensin aldosteron system in immunity and heart failure. In the past decade microRNAs (miRNAs), small non-coding RNAs that translationally repress protein synthesis by binding to partially complementary sequences of mRNA, have come to light as important regulators of several kinds of cardiovascular diseases including cardiac hypertrophy and heart failure. The involvement of differentially expressed miRNAs in the inflammation that occurs during the development of heart failure is still subject of investigation. Here, we summarize and comment on the first studies in this field and hypothesize on the putative involvement of certain miRNAs in heart failure. MicroRNAs have been shown to be critical regulators of cardiac function and inflammation. Future research will have to point out if dampening the immune response, and the miRNAs associated with it, during the development of heart failure is a therapeutically plausible route to follow

Ovarian stimulation for fertility treatments and risk of breast cancer: a matched cohort study

Abstract STUDY QUESTION Is there a difference in the breast cancer risk among women who underwent ART treatments compared to those who underwent medically assisted reproduction (MAR) infertility treatments or women of reproductive age in the general population? SUMMARY ANSWER The risk of breast cancer among women treated by ART was similar to the risk among women treated by MAR and women who did not undergo fertility treatments. WHAT IS KNOWN ALREADY Studies investigating breast cancer risk in women who have undergone fertility treatments have provided conflicting results. STUDY DESIGN, SIZE, DURATION A retrospective, population-based cohort study included women who underwent ART or MAR treatments and women who did not undergo fertility treatments from 1994 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Women who underwent ART were matched one to one with women who underwent MAR treatments and one to one with woman from the general population of reproductive age, by year of birth and year of first delivery or nulliparity status. MAR women were also matched to ART women by treatment initiation calendar year. All included women were members of Maccabi Healthcare Services. Data regarding demographics, fertility treatments, BRCA mutation and possible confounders were obtained from the computerized database of electronic health records. The incidence of breast cancer after fertility treatments was compared to the matched controls. MAIN RESULTS AND THE ROLE OF CHANCE Of 8 25 721 women of reproductive age, 32 366 women who underwent ART were matched with patients treated by MAR (n = 32 366) and 32 366 women of reproductive age. A total of 984 women (1.0%) were diagnosed with breast cancer (mean follow-up period, 9.1 ± 6.3 years; interquartile range [IQR], 3.8–13.7 years). The incidence rates of breast cancer per 10 000 person-years were 11.9 (95% CI, 10.7–13.3), 10.7 (95% CI, 9.6–11.9) and 10.7 (95% CI, 9.6–12.0) in the ART group, MAR group and general population, respectively. The crude risk for breast cancer was similar in the ART group compared with the general population (hazard ratio (HR) = 1.10, 95% CI, 0.94–1.28) and in the ART group compared with the MAR group (HR = 1.00, 95% CI, 0.86–1.16). Further adjustment for age, BMI, smoking, socioeconomic status and parity did not substantially impact the hazard rates for breast cancer (ART vs general population: HR = 1.10, 95% CI, 0.94–1.28; ART vs MAR: HR = 0.99, 95% CI, 0.85–1.16). Among women diagnosed with breast cancer, the prevalence of BRCA1/2 mutations and tumour staging did not differ between the ART, MAR and general population groups. Among women who underwent ART, no correlation was found between breast cancer and the number of ART cycles or the use of recombinant medications or urine-derived medications. LIMITATIONS, REASONS FOR CAUTION The mean age of women at the end of follow-up was only 42 years thus the study was not powered to detect potential differences in the risk of postmenopausal breast cancer. In addition, we did not sub-classify the exposed patients by the reason for infertility. WIDER IMPLICATIONS OF THE FINDINGS Breast cancer incidence following ART was comparable to that in the general population or following MAR. Women undergoing fertility treatments and their clinicians may be reassured about the safety of assisted reproduction technologies in terms of premenopausal breast cancer risk. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used and there are no competing interests. TRIAL REGISTRATION NUMBER N/A. </jats:sec

Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart

Aims The NLRP3 inflammasome is activated in the ischaemic heart promoting caspase-1 activation, inflammation, and cell death. Ischaemic injury establishes both a priming signal (transcription of inflammasome components) and a trigger (NLRP3 activation). Whether NLRP3 activation, without priming, induces cardiac dysfunction and/or failure is unknown. The aimof this studywas to assess the independent and complementary roles of the priming and the triggering signals in the heart, in the absence of ischaemia or myocardial injury. Methods and results WeusedmicewithmutantNLRP3 (constitutively active),NLRP3-A350V, under the control of tamoxifen-driven expres-sion of the Cre recombinase (Nlrp3-A350V/CreTmice). The mice were treated for 10 days with tamoxifen before mea-suring the activity of caspase-1, the effector enzyme in the inflammasome. Tamoxifen treatment induced th

Impact of mast cells in depression disorder: inhibitory effect of IL-37 (new frontiers)

The purpose of this article is to study the involvement of inflammatory mast cells (MCs) in depression which may be inhibited by IL-37. We evaluate mast cells in depression on the basis of our previous experimental data, and using the most relevant studies reported in the literature. Dysfunction of mood, feelings, and thoughts is a major risk factor for several metabolic diseases and may influence the physiology of the body leading to depression. Depression, present in mastocytosis, is an important endogenous process that promotes the activation of meningeal cell receptors through a low-grade neurogenic chronic inflammation, and MCs. Mast cells are localized along meningeal blood vessels and connective tissues, as well as between the ganglion cells and nerve fibers. They are present in the hypothalamus of mammalian brains capable of communication with nerves. MCs are classically activated by binding to IgE cross-link Fc\u3b5RI high-affinity receptor leading to release a plethora of mediators responsible for the generation of inflammatory cytokines. Corticotropin-releasing hormone (CRH), produced by MCs, has been found in microglial cells where it regulates immune cells and contributes to the pathogenesis of neurodegenerative diseases including depression. Inflammatory cytokines released by MCs aggravate depression and could be partially inhibited by IL-37. A detailed understanding of the interaction between the immune system, including MCs and depression, is necessary in order to address an effective therapy which could include IL-37. As a consequence, the concepts reviewed here have treatment implications