Search Results (9)

This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway. Full article

Atherosclerosis in a progressive disease that is systemic in nature, and hence the simultaneous presentation of coronary artery disease (CAD) and peripheral artery disease (PAD) is not uncommon. As clinically manifested PAD is associated with worse cardiovascular outcomes, the timely identification of subclinical atherosclerosis seems of utmost importance. Ultrasonography (US) is an ideal imaging modality for assessing PAD that is easy to use, accurate, widely available and avoids unnecessary exposure to radiation. Several US parameters have been proposed in the assessment of PAD, with varying prognostic usefulness, depending on disease location. The aim of this review is to summarize the most important evidence available on the association between US-detected atherosclerosis in different vascular sites and the presence and severity of CAD, as well as the impact of the early detection of PAD on the outcomes of patients presenting with CAD. Full article

Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE^−/− mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE^−/− mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE^−/−, but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions. Full article

Background: Anticancer treatments are improving the prognosis of patients fighting cancer. However, anticancer treatments may also increase the cardiovascular (CV) risk by increasing metabolic disorders. Atherosclerosis and atherothrombosis related to anticancer treatments may lead to ischemic heart disease (IHD), while direct cardiac toxicity may induce non-ischemic heart disease. Moreover, valvular heart disease (VHD), aortic syndromes (AoS), and advanced heart failure (HF) associated with CV risk factors and preclinical CV disease as well as with chronic inflammation and endothelial dysfunction may also occur in survivors of anti-carcer treatments. Methods: Public electronic libraries have been searched systematically looking at cardiotoxicity, cardioprotection, CV risk and disease, and prognosis after cardiac surgery in survivors of anticancer treatments. Results: CV risk factors and disease may not be infrequent among survivors of anticancer treatments. As cardiotoxicity of established anticancer treatments has been investigated and is frequently irreversible, cardiotoxicity associated with novel treatments appears to be more frequently reversible, but also potentially synergic. Small reports suggest that drugs preventing HF in the general population may be effective also among survivors of anticancer treatments, so that CV risk factors and disease, and chronic inflammation, may lead to indication to cardiac surgery in survivors of anticancer treatments. There is a lack of substantial data on whether current risk scores are efficient to predict prognosis after cardiac surgery in survivors of anticancer treatments, and to guide tailored decision-making. IHD is the most common condition requiring cardiac surgery among survivors of anticancer treatments. Primary VHD is mostly related to a history of radiation therapy. No specific reports exist on AoS in survivors of anticancer treatments. Conclusions: It is unclear whether interventions to dominate cancer- and anticancer treatment-related metabolic syndromes, chronic inflammation, and endothelial dysfunction, leading to IHD, nonIHD, VHD, HF, and AoS, are as effective in survivors of anticancer treatments as in the general population. When CV diseases require cardiac surgery, survivors of anticancer treatments may be a population at specifically elevated risk, rather than affected by a specific risk factor. Full article

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. Full article

Chronic obstructive pulmonary disease (COPD) and emphysema are characterized by functional and structural damage which increases the spaces for gaseous diffusion and impairs oxygen exchange. Here we explore the potential for hyperpolarized (HP) ³He MRI to characterize lung structure and function in a large-scale population-based study. Participants (n = 54) from the Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study, a nested case-control study of COPD among participants with 10+ packyears underwent HP ³He MRI measuring p_AO₂, apparent diffusion coefficient (ADC), and ventilation. HP MRI measures were compared to full-lung CT and pulmonary function testing. High ADC values (>0.4 cm²/s) correlated with emphysema and heterogeneity in p_AO₂ measurements. Strong correlations were found between the heterogeneity of global p_AO₂ as summarized by its standard deviation (SD) (p < 0.0002) and non-physiologic p_AO₂ values (p < 0.0001) with percent emphysema on CT. A regional study revealed a strong association between p_AO₂ SD and visual emphysema severity (p < 0.003) and an association with the paraseptal emphysema subtype (p < 0.04) after adjustment for demographics and smoking status. HP noble gas p_AO₂ heterogeneity and the fraction of non-physiological p_AO₂ results increase in mild to moderate COPD. Measurements of p_AO₂ are sensitive to regional emphysematous damage detected by CT and may be used to probe pulmonary emphysema subtypes. HP noble gas lung MRI provides non-invasive information about COPD severity and lung function without ionizing radiation. Full article

Cancer incidence and survivorship have had a rising tendency over the last two decades due to better treatment modalities. One of these is radiation therapy (RT), which is used in 20–55% of cancer patients, and its basic principle consists of inhibiting proliferation or inducing apoptosis of cancer cells. Classically, photon beam RT has been the mainstay therapy for these patients, but, in the last decade, proton beam has been introduced as a new option. This newer method focuses more on the tumor and affects less of the surrounding normal tissue, i.e., the heart. Radiation to the heart is a common complication of RT, especially in patients with lymphoma, breast, lung, and esophageal cancer. The pathophysiology is due to changes in the microvascular and macrovascular milieu that can promote accelerated atherosclerosis and/or induce fibrosis of the myocardium, pericardium, and valves. These complications occur days, weeks, or years after RT and the risk factors associated are high radiation doses (>30 Gy), concomitant chemotherapy (primarily anthracyclines), age, history of heart disease, and the presence of cardiovascular risk factors. The understanding of these mechanisms and risk factors by physicians can lead to a tailored assessment and monitorization of these patients with the objective of early detection or prevention of radiation-induced heart disease. Echocardiography is a noninvasive method which provides a comprehensive evaluation of the pericardium, valves, myocardium, and coronaries, making it the first imaging tool in most cases; however, other modalities, such as computed tomography, nuclear medicine, or cardiac magnetic resonance, can provide additional value. Full article

Nobiletin (NOB), one of polymethoxyflavone existing in citrus fruits, has been reported to exhibit a multitude of biological properties, including anti-inflammation, anti-oxidation, anti-atherosclerosis, neuroprotection, and anti-tumor activity. However, little is known about the anti-aging effect of NOB. The objective of this study was to determine the effects of NOB on lifespan, stress resistance, and its associated gene expression. Using Caenorhabditis elegans, an in vivo nematode model, we found that NOB remarkably extended the lifespan; slowed aging-related functional declines; and increased the resistance against various stressors, including heat shock and ultraviolet radiation. Also, NOB reduced the effects of paraquat stressor on nematodes and scavenged reactive oxygen species (ROS). Furthermore, gene expression revealed that NOB upregulated the expression of sod-3, hsp-16.2, gst-4, skn-1, sek-1, and sir-2.1, which was suggested that anti-aging activity of NOB was mediated most likely by activation of the target genes of the transcription factors including dauer formation (DAF)-16, heat-shock transcription factor (HSF)-1, and skinhead (SKN)-1. In summary, NOB has potential application in extension of lifespan, and its associated healthspan and stress resistances. Full article

Coronary artery calcium (CAC) has been advocated as one of the strongest cardiovascular risk prediction markers. It performs better across a wide range of Framingham risk categories (6%–10% and 10%–20% 10-year risk categories) and also helps in reclassifying the risk of these subjects into either higher or lower risk categories based on CAC scores. It also performs better among population subgroups where Framingham risk score does not perform well, especially young subjects, women, family history of premature coronary artery disease and ethnic differences in coronary risk. The absence of CAC is also associated with excellent prognosis, with 10-year event rate of 1%. Studies have also compared with other commonly used markers of cardiovascular disease risk such as Carotid intima-media thickness and highly sensitive C-reactive protein. CAC also performs better compared with carotid intima-media thickness and highly sensitive C-reactive protein in prediction of coronary heart disease and cardiovascular disease events. CAC scans are associated with relatively low radiation exposure (0.9–1.1 mSv) and provide information that can be used not only for risk stratification but also can be used to track the progression of atherosclerosis and the effects of statins. Full article