Read it in depth! Cardiovascular disease may be closely related to cancer!

August 21, 2020 // -- Researchers are now slowly realizing that the systemic environment of the host body may promote cancer progression and be affected by cancer, but our understanding of this interaction is still in its infancy, for example, breast cancer patients have an increased risk of cardiovascular disease, but researchers do not know whether cardiovascular disease events It can also affect cancer progression, and using mouse models and human data, researcher Koelwyn et al. investigated the relationship between the two and found that myocardial infarction may promote breast tumor growth and increase the risk of cancer-specific death.
researchers studied the mouse model of the same gene breast cancer (E0771 model) and induced myocardial infarction (MI) in the mouse model by ligation of the left coronary artery left frontal descending three days after implanting the tumor into its breast fat pad Compared to "fake surgery", MI's induction increases the size and weight of the tumor within 20 days, and the researchers have not observed the effects on heart function or the body's clinical response to MI, suggesting that such changes may not drive the effect on tumor growth.
when the researchers analyzed immune cells in the tumor micro-environment, they found that there were more CD45 plus white blood cells in mouse model tumors after MI than in fake surgery, including CD11b plus Ly6G. Ly6Chi monocytes, while the number of macrophages, neutral granulocytes, or degenerative cells may not have changed, and monocyte bone marrow-derived inhibitory cells (mMDSCs, which limit the immersion of T-cells) are CD11b-Ly6G? In the sub-group of Ly6Chi cells, the researchers say, E0771 tumors in mice tend to have fewer intra-tumor cells after MI occurs, and in these tumors, a higher proportion of T cells may be immunosuppressive regulatory T cells (Treg cells).
image source: sagaciousnewsnetwork.comMI is thought to increase the level of circulating Ly6Chi monocytes in mice, an increase that usually occurs after 12 days, however, in mice with E0771 tumors, MI circulates in the body after it occurs The level of monocytes is maintained, and the increase in the level of these cells recruited into the tumor does not seem to be inherent in single-nucleocytes, as the monocytes marked after MI are transferred from non-tumor mice to mice carrying tumors, resulting in an increase in the level at which monocytes are recruited into the tumor.
the removal of Ly6Chi monocytes indicates that these cells are necessary to increase tumor growth after MI occurs, and when these cells are lacking, the proportion of tumor-immersed T-cells decreases, while cd8-plus cytotoxic T-cell levels increase, and separation occurs Ly6Chi monocytes in MICE may be more effective in inhibiting CD8-plus T cell activation, suggesting that MI-exposed monocytes can function as mMDSCs and effectively suppress the body's anti-tumor immunity.
In order to study the molecular mechanisms by which MI-induced monocytes may promote cancer progression, the researchers analyzed the transcriptional group characteristics of tumors and monocyte groups, and the tumors in mice nine days after MI increased the expression of genes that encode the polymer factor, including Cxcl13, while the monocytes from the mouse body also increased the expression of genes that encode the polymer receptor, including Cxcr5, which encodes the CXCL13 receptor; After conducting RNA sequencing analysis of mMDSCs isolated in mice with MI 17 days after MI or under false surgery, the researchers found significant changes in the expression of 235 genes in these cells, many of which were involved in converting MI-exposed cells into more immunosuppressive states, and similar changes were observed in Ly6Chi monocytes isolated from mice before tumor size changed. Changes in the
transcription group may be related to changes in the accessability of monocyte chromatin, and the accessability of chromatin after implantation into the bone marrow of mice with natural MI is maintained, and the results suggest that MI induces persistent exogenetic reprogramming of monocytes to move them towards immunosuppression.
To prove that these findings are not unique to mouse models, the researchers also showed that MI increased tumor growth in mmTV-PyMT mouse models with spontaneous breast cancer, and after a retrospective analysis of breast cancer patients who did not have cardiovascular disease or risk factors at the time of cancer diagnosis, the researchers noted that cardiovascular events after cancer diagnosis increased the risk of cancer recurrence and cancer-specific death.
the researchers concluded that systemic changes in the body induced by MI may accelerate the progression of breast cancer, while the study also highlights the importance of understanding the biological effects of co-disease on cancer incidence in patients.
() References: Koelwyn, G.J., Newman, A.A.C., Afonso, M.S. et al. Myocardial infarction accelerates breast cancer via innate immune reprogramming. Nat Med (2020). doi:10.1038/s41591-020-0964-7. Seton-Rogers, S. Cardiovascular and cancer communicate. Nat Rev Cancer (2020). doi:10.1038/s41568-020-0294-6.