Radiation-Induced Coronary Artery Disease

Tracy, Gerald P.; Brown, Douglas; Johnson, Lewis W.; Gottlieb, Arlan J.

doi:10.1001/jama.1974.03230380028017

Cited by 65 publications

(9 citation statements)

References 8 publications

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“…For example, local breast or thyroid irradiation is associated with late development of coronary or carotid atherosclerosis, respectively. 35,36 However, the extent of DNA damage is likely to determine the subsequent consequences. Increasing doses of radiation promote atherosclerosis in ApoE −/− mice, particularly an inflammatory and thrombotic phenotype, 37,38 whereas intracoronary brachytherapy was used to prevent or treat in-stent stenosis.…”

Section: Dna Damage In Atherosclerosis 825mentioning

confidence: 99%

Effects of DNA Damage in Smooth Muscle Cells in Atherosclerosis

Gray

Kumar

Figg

et al. 2015

Circulation Research

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Rationale: DNA damage and the DNA damage response have been identified in human atherosclerosis, including in vascular smooth muscle cells (VSMCs). However, although double-stranded breaks (DSBs) are hypothesized to promote plaque progression and instability, in part, by promoting cell senescence, apoptosis, and inflammation, the direct effects of DSBs in VSMCs seen in atherogenesis are unknown. Objective: To determine the presence and effect of endogenous levels of DSBs in VSMCs on atherosclerosis. Methods and Results: Human atherosclerotic plaque VSMCs showed increased expression of multiple DNA damage response proteins in vitro and in vivo, particularly the MRE11/RAD50/NBS1 complex that senses DSB repair. Oxidative stress–induced DSBs were increased in plaque VSMCs, but DSB repair was maintained. To determine the effect of DSBs on atherosclerosis, we generated 2 novel transgenic mice lines expressing NBS1 or C-terminal deleted NBS1 only in VSMCs, and crossed them with apolipoprotein E −/− mice. SM22α-NBS1/apolipoprotein E −/− VSMCs showed enhanced DSB repair and decreased growth arrest and apoptosis, whereas SM22α-(ΔC)NBS1/apolipoprotein E −/− VSMCs showed reduced DSB repair and increased growth arrest and apoptosis. Accelerating or retarding DSB repair did not affect atherosclerosis extent or composition. However, VSMC DNA damage reduced relative fibrous cap areas, whereas accelerating DSB repair increased cap area and VSMC content. Conclusions: Human atherosclerotic plaque VSMCs show increased DNA damage, including DSBs and DNA damage response activation. VSMC DNA damage has minimal effects on atherogenesis, but alters plaque phenotype inhibiting fibrous cap areas in advanced lesions. Inhibiting DNA damage in atherosclerosis may be a novel target to promote plaque stability.

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Section: Dna Damage In Atherosclerosis 825mentioning

confidence: 99%

Effects of DNA Damage in Smooth Muscle Cells in Atherosclerosis

Gray

Kumar

Figg

et al. 2015

Circulation Research

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“…One reason is that there are very few existing model systems by which the late effects on the vasculature can be evaluated quantitatively. From clinical observations after high doses, we know that radiation damage to the vascular system is a contributing factor to degenerative changes in many tissues and can be a significant factor in the patient's late responses to radiotherapy (2)(3)(4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Late Effects of Heavy Charged Particles on the Fine Structure of the Mouse Coronary Artery

Yang¹,

Ainsworth²

1982

Radiation Research

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“…Occurrence of coronary heart disease following megavoltage therapy to the mediastinum has been reported in at least eight other patients with Hodgkin's disease (3, 5, 6, 9, 1 I , 12,14) (Table I). The mean age of these patients was 28 years (range 15-41), the mean time from irradiation to heart disease Table I tion showed severe atherosclerosis of the coronary arteries and two cases showed thrombosis of the anterior descending branch of the left coronary artery (3,6).…”

Section: Discussionmentioning

confidence: 97%

Coronary Heart Disease—a Possible Risk in Megavoltage Therapy?

Rasmussen¹,

Døssing²,

Walbom-Jørgensen³

1978

Journal of Internal Medicine

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ABSTRACT. A 21‐year old man died of an extensive anteroseptal myocardial infarction 16 months after receiving megavoltage radiotherapy to a mantle field for Hodgkin's disease stage PS IA confined to the midcervical lymph nodes on the left side of the neck. Post mortem findings revealed severe atherosclerotic changes in the coronary arteries. This case and a review of the literature suggest that irradiation to the heart may induce or accelerate atherosclerosis of the epicardial vessels. This should be taken into consideration when starting prophylactic irradiation to the mantle field in patients with Hodgkin's disease stage IA without obvious involvement of the mediastinun. Histologic examination of the heart and coronary vessels should be performed in any fatal case after megavoltage therapy involving the heart.

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Radiation-Induced Coronary Artery Disease

Cited by 65 publications

References 8 publications

Effects of DNA Damage in Smooth Muscle Cells in Atherosclerosis

Effects of DNA Damage in Smooth Muscle Cells in Atherosclerosis

Late Effects of Heavy Charged Particles on the Fine Structure of the Mouse Coronary Artery

Coronary Heart Disease—a Possible Risk in Megavoltage Therapy?

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