Chronic hypertriglyceridemia in young watanabe heritable hyperlipidemic rabbits impairs endothelial and medial smooth muscle function

Shishido, Tetsuro; Tasaki, Katsunari; Takeishi, Yasuchika; Takasaki, Satoshi; Miyamoto, Takuya; Itoh, Makoto; Takahashi, Hitomi; Ito, Tsunekata; Katano, Yumi; Wakabayashi, Ichiro; Tomoike, Hitonobu

doi:10.1016/j.lfs.2003.08.018

Cited by 14 publications

(16 citation statements)

References 30 publications

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“…Similarly, Hasdai et al (40) showed that pigs fed a hypercholesterolemic diet for 10 weeks had reduced vasorelaxation to bradykinin, abnormal responses to the endothelin B-receptor agonist sarafotoxin 6c (41), and impaired arteriolar relaxation to insulin-like growth factor (42). Impairments in smooth muscle function in the setting of hypercholesterolemia have also been demonstrated by Shishido and colleagues (95) in hypercholesterolemic rabbit aortae, in addition to endothelial dysfunction.…”

Section: Effects Of Hypercholesterolemiamentioning

confidence: 86%

Therapeutic Angiogenesis in Diabetes and Hypercholesterolemia: Influence of Oxidative Stress

Boodhwani

Sellke

2009

Antioxidants & Redox Signaling

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Despite significant improvements in the medical, percutaneous, and surgical management, numerous patients are first seen with non-revascularizable coronary artery disease (CAD). The growth of new blood vessels to improve myocardial perfusion (i.e., therapeutic angiogenesis) is an attractive treatment option for these patients. However, the successes of angiogenic therapy, observed in preclinical studies, have not been realized in clinical trials. Increasing evidence suggests that this discrepancy between animal and human studies may be due to the nature of the substrate, or the molecular and cellular environment within which the angiogenic agent acts. Antiangiogenic influences, including endothelial dysfunction, hypercholesterolemia, and diabetes, are present in virtually all patients with advanced CAD. Recent studies have better characterized the abnormalities associated with these disease states, providing novel targets for intervention. These substrate-modifying interventions can potentially enhance the response to protein-, gene-, or cell-based angiogenic therapy. In this review, we discuss key aspects of the angiogenic process and the pathophysiologic and molecular mechanisms that contribute to an impaired angiogenic response in the setting of endothelial dysfunction, hypercholesterolemia, and diabetes, with a focus on the role of oxidative stress. Last, we briefly explore substrate modifying agents that have been evaluated in preclinical and clinical studies to improve the angiogenic response.

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Section: Effects Of Hypercholesterolemiamentioning

confidence: 86%

Therapeutic Angiogenesis in Diabetes and Hypercholesterolemia: Influence of Oxidative Stress

Boodhwani

Sellke

2009

Antioxidants & Redox Signaling

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“…The lack of impairment of endothelium-dependent vasodilation in the WHHL rabbit abdominal aorta in the present study may also be due to a lesser degree of atherosclerosis. Moreover, our recent study demonstrated that attenuation of endothelium-dependent relaxation of the WHHL rabbit thoracic aorta, which displayed markedly large atherosclerotic plaques, was observed only in those animals with hypertriglyceridemia (Shishido et al, 2004), suggesting that hypertriglyceridemia aggravates hypercholesterolemia-induced functional impairment of endothelial cells. The contractile force of the aorta in response to angiotensin II was not affected by pretreatment with diclofenac, a cyclooxygenase inhibitor, while that in the presence of diclofenac was also lower in the WHHL group than in the control group.…”

Section: Discussionmentioning

confidence: 96%

“…On the other hand, little is known about changes in angiotensin II contraction in arteries of WHHL rabbits. Our recent study has shown that the thoracic aorta isolated from WHHL rabbits displayed a decreased contractile response to angiotensin II, while its type 1 (AT1) receptor expression was increased in the aorta of young WHHL rabbits at 3-4 months of age (Shishido et al, 2004). The present study is the first to demonstrate that angiotensin II-induced contraction was also specifically attenuated in the abdominal aorta of WHHL rabbits, while their 5-hydroxytryptamine-induced contraction was not significantly different from the aorta of control rabbits.…”

Section: Discussionmentioning

confidence: 99%

“…The above findings suggest that the decrease in the angiotensin II contraction in the WHHL rabbit aorta is mainly due to an abnormality in smooth muscle contractility, and is not due to changes in the release of vasodilatory substances from the vessel wall. AT1 receptor expression has rather been shown to be up-regulated in the thoracic aorta of WHHL rabbits (Shishido et al, 2004). Thus, further study including AT1 receptor coupling with downstream signals in vascular smooth muscle cells is needed to clarify the mechanism involved in the attenuated contractile response to angiotensin II in the WHHL aorta.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, little is known about the vascular response of the abdominal aorta isolated from WHHL rabbits. We have recently reported that angiotensin II-induced contraction was attenuated in the thoracic aorta isolated from WHHL rabbits (Shishido et al, 2004). However, the detailed mechanism of this attenuation of angiotensin II contraction still remains to be determined.…”

Section: Introductionmentioning

confidence: 98%

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Diminution of angiotensin II-induced contraction of the abdominal aorta isolated from Watanabe heritable hyperlipidemic rabbits

Tasaki

Wakabayashi

Shishido

et al. 2005

J. Smooth Muscle Res.

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The purpose of this study was to investigate the changes in vasocontractile responses in atherosclerosis, using abdominal aortic strips isolated from Watanabe heritable hyperlipidemic (WHHL) rabbits and Japanese White (control) rabbits. The aortic strips from WHHL rabbits showed a significantly lower contractile response to angiotensin II than that in strips from control rabbits. The contractile responses to phenylephrine and 5-hydroxytryptamine were not different in WHHL and control groups. The contractile response to angiotensin II was higher in endothelium-denuded aortic strips than in endothelium-intact strips, but to a greater extent in the control group than in the WHHL group. The contractile response to angiotensin II in the absence of the endothelium was also lower in the WHHL group than in the control group. Pretreatment with N G -nitro-Larginine significantly increased the contractile response to angiotensin II in the endothelium-intact aortic strips in both the WHHL and control groups, while pretreatment with diclofenac did not affects the aortic contractile response to angiotensin II. The contractile responses to angiotensin II in the presence of N G -nitro-L-arginine and diclofenac were lower in the WHHL group than in the control group. The contractile response to angiotensin II in the presence of PD123319 was also lower in the WHHL group than in the control group. Endothelium-dependent relaxation by acetylcholine occurred to the some extent in the WHHL and control groups. These results suggest that the WHHL rabbit abdominal aorta displays attenuated angiotensin II-induced contraction, mainly due to an abnormality in the angiotensin II-specific contractile pathway of the medial smooth muscle.

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Association between metabolic syndrome and pelvic organ prolapse severity

et al. 2014

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Introduction and hypothesisAs in the case of cardiovascular and metabolic diseases, the prevalence of pelvic organ prolapse (POP) has been rising with the increasing proportion of elderly women in the population. The purpose of the present cross-sectional study was to evaluate the components of metabolic syndrome (MS) in urogynecological patients with a variable POP severity.MethodsThe MS risk factors (elevated waist circumference, elevated triglycerides, decreased high-density lipoprotein cholesterol, elevated blood pressure, hyperglycemia) were assessed in 100 women who were referred to our urogynecological center with pelvic floor disorders (PFD). POP was evaluated with the Pelvic Organ Prolapse Quantification system (POP-Q).ResultsThe χ2 test revealed that the diagnosis of MS and the presence of elevated triglycerides increased with the overall POP-Q stage. The other MS risk factors were not significantly associated with the overall POP-Q stage. MS and elevated triglycerides were predictors of the POP-Q stage ≥III [odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.5–8.2 for MS and OR 3.4, 95 % CI 1.4–8.2 for elevated triglycerides, p < 0.01].ConclusionsThe diagnosis of MS and the presence of elevated triglycerides may be associated with the severity of POP in urogynecological patients. Longitudinal studies are required to assess whether the MS risk factors might predict the progression of POP and whether elimination of the risk factors might improve the prognosis in POP patients.

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Chronic hypertriglyceridemia in young watanabe heritable hyperlipidemic rabbits impairs endothelial and medial smooth muscle function

Cited by 14 publications

References 30 publications

Therapeutic Angiogenesis in Diabetes and Hypercholesterolemia: Influence of Oxidative Stress

Therapeutic Angiogenesis in Diabetes and Hypercholesterolemia: Influence of Oxidative Stress

Diminution of angiotensin II-induced contraction of the abdominal aorta isolated from Watanabe heritable hyperlipidemic rabbits

Association between metabolic syndrome and pelvic organ prolapse severity

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