Comparison of <i>β</i>-aminopropionitrile-induced aortic dissection model in rats by different administration and dosage

Li, Jiasi; Li, Haiyan; Wang, Liang; Zhang, Lei; Jing, Zaiping

doi:10.1177/1708538113478741

Cited by 26 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with another study (37). The mortality rate in the present study was lower compared with some studies (12,38) as older rats were used in the present study instead of 3-week-old rats. Tatsuo Kawai et al (11) used a similar protocol in modeling abdominal aortic aneurysm and observed similar mortality.…”

Section: Discussioncontrasting

confidence: 53%

The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the�expression of the TGFβ receptor ALK5 in aorta remodeling

Wang

et al. 2020

Mol Med Report

View full text Add to dashboard Cite

The sympathetic system is involved in the arterial diseases, but its mechanism remains poorly understood. The present study aimed to explore the impact of the sympathetic neurotransmitter norepinephrine (ne) on transforming growth factor (TGF) β signaling and the role of ne in aortic remodeling. Guanethidine was used to induce a regional chemical sympathetic denervation (cSd) in angiotensin ii (angii) and β-aminopropionitrile (BaPn)-induced aortic aneurysm models. The diameter of the aorta was measured, and elastic fiber staining was performed. TGFβ type i receptor kinase (alK5) expression in rat aortic ne-treated vascular smooth muscle cells (VSMcs) was detected by reverse transcription-quantitative Pcr and western blotting. The effects of ne and alK5 overexpression on migration, proliferation, apoptosis and TGFβ signaling were also evaluated. Furthermore, adrenergic receptor blockers were used to determine which receptor was involved in the modulation on TGFβ signaling by ne. The results of the present study demonstrated that cSd protected rats from angii+BaPn-induced aortic remodeling and aneurysm formation. compared with the control group, ne inhibited VSMc proliferation and migration, but promoted apoptosis by suppressing alK5 expression, reversing the effects of TGFβ signaling through the suppression of the SMad-dependent canonical pathway and promotion of the non-canonical pathway. These effects were prevented by alK5 overexpression. The inhibition of α-or β-adrenergic receptors alleviated the ne-mediated suppression of alK5 expression. in conclusion, regional cSd protected rats from aortic aneurysm. ne inhibited SMad2/3-dependent TGFβ signaling by suppressing alK5 expression, which may serve an important role in VSMc biological functions. Both α-and β-adrenergic receptors were involved in the regulation of alK5 expression by ne. abnormal sympathetic innervation of the aorta may be used as a therapeutic target in aortic diseases.

show abstract

Section: Discussioncontrasting

confidence: 53%

The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the�expression of the TGFβ receptor ALK5 in aorta remodeling

Wang

et al. 2020

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…and ). Others have observed similar discontinuities in BAPN dose effects in vascular tissues . BAPN does not alter existing cross‐links.…”

Section: Discussionmentioning

confidence: 68%

“…Others have observed similar discontinuities in BAPN dose effects in vascular tissues. (44) BAPN does not alter existing cross-links. Thus, at the end of the experiment, each mouse is a hybrid of normal and cross-link-deficient tissues in proportions determined by the rates of tissue apposition and removal.…”

Section: Discussionmentioning

confidence: 96%

Bone Fracture Toughness and Strength Correlate With Collagen Cross-Link Maturity in a Dose-Controlled Lathyrism Mouse Model

McNerny

Gong

Morris

et al. 2014

Journal of Bone and Mineral Research

120

117

View full text Add to dashboard Cite

Collagen cross-linking is altered in many diseases of bone, and enzymatic collagen cross-links are important to bone quality as evidenced by losses of strength following lysyl oxidase inhibition (lathyrism). We hypothesized that cross-links also contribute directly to bone fracture toughness. A mouse model of lathyrism using subcutaneous injection of up to 500mg/kg β-aminopropionitrile (BAPN) was developed and characterized (60 animals across 4 dosage groups). Three weeks of 150 or 350 mg/kg BAPN treatment in young growing mice significantly reduced cortical bone fracture toughness, strength, and pyridinoline cross-link content. Ratios reflecting relative cross-link maturity were positive regressors of fracture toughness (HP/[DHLNL+HLNL] r2=0.208, p<0.05; [HP+LP]/[DHNL+HLNL] r2=0.196, p<0.1), whereas quantities of mature pyridinoline cross-links were significant positive regressors of tissue strength (lysyl pyridinoline r2=0.159, p=0.014; hydroxylysyl pyridinoline r2=0.112, p<0.05). Immature and pyrrole cross-links, which were not significantly reduced by BAPN, did not correlate with mechanical properties. The effect of BAPN treatment on mechanical properties was dose specific, with the greatest impact found at the intermediate (350mg/kg) dose. Calcein labeling was used to define locations of new bone formation, allowing for the identification of regions of normally cross-linked (preexisting) and BAPN treated (newly formed, cross-link-deficient) bone. Raman spectroscopy revealed spatial differences due to relative tissue age and effects of cross-link inhibition. Newly deposited tissues had lower mineral/matrix, carbonate/phosphate and Amide I cross-link (matrix maturity) ratios compared to preexisting tissues. BAPN treatment did not affect mineral measures, but significantly increased the cross-link (matrix maturity) ratio compared to newly formed control tissue. Our study reveals that spatially localized effects of short term BAPN cross-link inhibition can alter the whole bone collagen cross-link profile to a measureable degree, and this cross-link profile correlates with bone fracture toughness and strength. Thus, cross-link profile perturbations associated with bone disease may provide insight into bone mechanical quality and fracture risk.

show abstract

“…It is also established that irreversible inhibition of lysyl oxidase activity by administration of β-aminopropionitrile (BAPN) induces thoracic aortic aneurysms and dissections in both young turkeys and rats. 16–21 The aortic pathology in BAPN-treated young rats shows features of medial degeneration, including elastin degradation, thickening of the medial layer, and SMC apoptosis. 22 Thus, inhibition of lysyl oxidase activity postnatally also induces thoracic aortic disease.…”

Section: Discussionmentioning

confidence: 99%

LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections

Guo

Regalado

Gong

et al. 2016

Circulation Research

185

137

View full text Add to dashboard Cite

Rationale Mutations in several genes have been identified that are responsible for approximately 25% of families with familial thoracic aortic aneurysms and dissections (TAAD). However, the causative gene remains unknown in 75% of families. Objectives To identify the causative mutation in families with autosomal dominant inheritance of TAAD. Methods and Results Exome sequencing was used to identify the mutation responsible for a large family with TAAD. A heterozygous rare variant, c.839G>T (p.Ser280Arg), was identified in LOX, encoding a lysyl oxidase, that segregated with disease in the family. Sanger and exome sequencing was performed to investigate mutations in candidate genes in an additional 410 probands from unrelated families. Additional LOX rare variants that segregated with disease in families were identified, including c.125G>A (p.Trp42*), c.604G>T (p.Gly202*), c.743C>T (p.Thr248Ile), c.800A>C (p.Gln267Pro), and c.1044T>A (p.Ser348Arg). The altered amino acids cause haploinsufficiency for LOX or are located at a highly conserved LOX catalytic domain, which is relatively invariant in the population. Expression of the LOX variants p.Ser280Arg and p.Ser348Arg had significantly lower lysyl oxidase activity when compared with the wild type protein. Individuals with LOX variants had fusiform enlargement of the root and ascending thoracic aorta, leading to ascending aortic dissections. Conclusions These data, along with previous studies showing the deficiency of LOX in mice or inhibition of lysyl oxidases in turkeys and rats causes aortic dissections, support the conclusion that rare genetic variants in LOX predispose to thoracic aortic disease.

show abstract

Comparison of β-aminopropionitrile-induced aortic dissection model in rats by different administration and dosage

Cited by 26 publications

References 12 publications

The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the�expression of the TGFβ receptor ALK5 in aorta remodeling

The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the�expression of the TGFβ receptor ALK5 in aorta remodeling

Bone Fracture Toughness and Strength Correlate With Collagen Cross-Link Maturity in a Dose-Controlled Lathyrism Mouse Model

LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections

Contact Info

Product

Resources

About