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Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

No MeSH data available.


Related in: MedlinePlus

Simvastatin mitigates cardiac morphological changes. Sections of the heart stained with Trichrome showing increased peri-arterial fibrosis in small caliber coronary vessel 120 days after TBI with 10 Gy, compared with a comparable vessel in an age-matched nonirradiated control rat. Fibrosis appears as blue using trichrome staining. TBI exposure to 10 Gy, followed by Sim treatment (TBI + Sim), mitigated against increased mural fibrosis in coronary arteries and blockage of the vessel lumen. Three hearts were studied in each group. TBI, total body irradiation.
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fig03: Simvastatin mitigates cardiac morphological changes. Sections of the heart stained with Trichrome showing increased peri-arterial fibrosis in small caliber coronary vessel 120 days after TBI with 10 Gy, compared with a comparable vessel in an age-matched nonirradiated control rat. Fibrosis appears as blue using trichrome staining. TBI exposure to 10 Gy, followed by Sim treatment (TBI + Sim), mitigated against increased mural fibrosis in coronary arteries and blockage of the vessel lumen. Three hearts were studied in each group. TBI, total body irradiation.

Mentions: TBI resulted in an increase in peri-arterial sclerosis of small caliber intramural coronary vessels at 120 days, compared with age-matched controls. Affected vessels had partial to complete luminal sclerosis due to concentric laminar thickening of the vessel walls due to the accumulation of amphophilic matrix material between layers of hyperplastic and vacuolated smooth myocytes. Cardiomyocytes from TBI-treated rats remained normal in appearance (Fig.3). Trichrome staining revealed peri-arterial fibrosis and irregular collagen deposition around the penetrating coronary vessels of hearts from irradiated rats. Control hearts had symmetrical penetrating vessels with only less collagen and fibrosis (Fig.3). Simvastatin partially mitigated the appearance of TBI-induced fibrosis of the penetrating coronary vessels. Simvastatin alone had no effect on the density of these coronary vessels.


Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Simvastatin mitigates cardiac morphological changes. Sections of the heart stained with Trichrome showing increased peri-arterial fibrosis in small caliber coronary vessel 120 days after TBI with 10 Gy, compared with a comparable vessel in an age-matched nonirradiated control rat. Fibrosis appears as blue using trichrome staining. TBI exposure to 10 Gy, followed by Sim treatment (TBI + Sim), mitigated against increased mural fibrosis in coronary arteries and blockage of the vessel lumen. Three hearts were studied in each group. TBI, total body irradiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492761&req=5

fig03: Simvastatin mitigates cardiac morphological changes. Sections of the heart stained with Trichrome showing increased peri-arterial fibrosis in small caliber coronary vessel 120 days after TBI with 10 Gy, compared with a comparable vessel in an age-matched nonirradiated control rat. Fibrosis appears as blue using trichrome staining. TBI exposure to 10 Gy, followed by Sim treatment (TBI + Sim), mitigated against increased mural fibrosis in coronary arteries and blockage of the vessel lumen. Three hearts were studied in each group. TBI, total body irradiation.
Mentions: TBI resulted in an increase in peri-arterial sclerosis of small caliber intramural coronary vessels at 120 days, compared with age-matched controls. Affected vessels had partial to complete luminal sclerosis due to concentric laminar thickening of the vessel walls due to the accumulation of amphophilic matrix material between layers of hyperplastic and vacuolated smooth myocytes. Cardiomyocytes from TBI-treated rats remained normal in appearance (Fig.3). Trichrome staining revealed peri-arterial fibrosis and irregular collagen deposition around the penetrating coronary vessels of hearts from irradiated rats. Control hearts had symmetrical penetrating vessels with only less collagen and fibrosis (Fig.3). Simvastatin partially mitigated the appearance of TBI-induced fibrosis of the penetrating coronary vessels. Simvastatin alone had no effect on the density of these coronary vessels.

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

No MeSH data available.


Related in: MedlinePlus