Tissue Reactions and Mechanism in Cardiovascular Diseases Induced by Radiation

Abstract

The long-term survival rate of cancer patients has been increasing as a result of advances in treatments and precise medical management. The evidence has accumulated that the incidence and mortality of non-cancer diseases have increased along with the increase in survival time and long-term survival rate of cancer patients after radiotherapy. The risk of cardiovascular disease as a radiation late effect of tissue damage reactions is becoming a critical challenge and attracts great concern. Epidemiological research and clinical trials have clearly shown the close association between the development of cardiovascular disease in long-term cancer survivors and radiation exposure. Experimental biological data also strongly supports the above statement. Cardiovascular diseases can occur decades post-irradiation, and from initiation and development to illness, there is a complicated process, including direct and indirect damage of endothelial cells by radiation, acute vasculitis with neutrophil invasion, endothelial dysfunction, altered permeability, tissue reactions, capillary-like network loss, and activation of coagulator mechanisms, fibrosis, and atherosclerosis. We summarize the most recent literature on the tissue reactions and mechanisms that contribute to the development of radiation-induced cardiovascular diseases (RICVD) and provide biological knowledge for building preventative strategies.

Cancer and Non-Cancer Effects Following Ionizing Irradiation

“…A growing body of epidemiological evidence has suggested elevated radiation risks of cardiovascular diseases (especially ischemic heart disease and stroke) [ 30 , 31 , 32 , 33 ]; however, the manifestations (in particular at low or moderate doses, and at low dose rates) and mechanistic underpinnings of this remain incompletely understood [ 9 , 34 , 35 ]. Nabialek-Trojanowska et al [ 12 ] carried out speckle-tracking echocardiography in 12 patients at a median of 51 months after radiotherapy for mediastinal lymphoma, concluding that radiation exposure of the heart substructures is correlated with cardiac dysfunction (e.g., left ventricular global or anterior longitudinal strain).…”

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy

“…Radiation tissue reactions are based on cellular responses, referring to the detriment arising from noncancer effects of radiation on health, which were previously called ‘deterministic effects’ [ 36 , 37 , 38 ]. The manifestations of tissue damage and reactions vary from one tissue to another depending not only on irradiation doses but also on the cellular composition, proliferation rate, and intrinsic mechanisms of responses to radiation, which may be highly tissue specific.…”

“…During the radiotherapy process, tumor cells can undergo a series of complex biological responses and changes, consequently resulting in cancer cell death and tumor suppression. However, when cancer cells develop resistance to ionizing radiation or severe side effects are induced in normal tissues, the effectiveness of radiation therapy is greatly compromised [ 16 , 36 , 63 ]. There are different molecular aspects of the mechanisms for the radioresistance of tumors, including intrinsic genetic or epigenetic changes in cancer cells, the microenvironment of tumors, the existence of a small number of radioresistant cancer stem cells, etc.…”

Cardiovascular Toxicities of Radiation Therapy and Recommended Screening and Surveillance

“…2023, 10, 447 2 of 12 they deposit high amounts of energy that directly damage the deoxyribonucleic acid (DNA) of cells, thereby blocking their proliferative abilities [3]. Radiation can also indirectly cause cell death through the creation of free radicals that can, in turn, lead to DNA damage [3]. As the energy passes through tissues, it is not able to distinguish cancer cells from nearby healthy cells.…”

“…High doses and large fields of radiation are associated with inflammation, injury, and death of the myocardial cells. As a result, the myocardium is infiltrated by myofibroblasts which leads to an increase in collagen deposition [3,4]. The myocardium becomes stiff and fibrosed, resulting in a restrictive cardiomyopathy with diastolic dysfunction [3,4].…”