Azelnidipine suppresses the progression of aortic aneurysm in wild mice model through anti-inflammatory effects

Kurobe, Hirotsugu; Matsuoka, Yuki; Hirata, Yoichiro; Sugasawa, Noriko; Maxfield, Mark W.; Sata, Masataka; Kitagawa, Tetsuya

doi:10.1016/j.jtcvs.2013.02.073

Cited by 25 publications

(24 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that azelnidipine has the effects of anti-inflammation and antioxidant in mouse aneurysmal models [20], [21]. Therefore, we next examined the effects of antioxidants, DPI and tempol on cyclic mechanical stretch-induced RASMC death.…”

Section: Resultsmentioning

confidence: 99%

“…Under the present conditions, the protective effects of azelnidipine on RASMCs seemed to be different from its antihypertensive effects, because the cyclic mechanical stretch was applied. It has been reported that azelnidipine exhibited a suppressing effect on aneurysm development in mouse models of aortic aneurysms, which was thought to be independent of its antihypertensive action [20], [21]. Those researchers considered that azelnidipine suppressed the progression of aortic aneurysm through both anti-inflammatory [20] and antioxidant mechanisms [21].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Azelnidipine Inhibits Cultured Rat Aortic Smooth Muscle Cell Death Induced by Cyclic Mechanical Stretch

et al. 2014

View full text Add to dashboard Cite

Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. Clarifying the detailed mechanism for aortic dissection is of great significance for establishing effective pharmacotherapy for this high mortality disease. In the present study, we evaluated the influence of biomechanical stretch, which mimics an acute rise in blood pressure using an experimental apparatus of stretching loads in vitro, on rat aortic smooth muscle cell (RASMC) death. Then, we examined the effects of azelnidipine and mitogen-activated protein kinase inhibitors on mechanical stretch-induced RASMC death. The major findings of the present study are as follows: (1) cyclic mechanical stretch on RASMC caused cell death in a time-dependent manner up to 4 h; (2) cyclic mechanical stretch on RASMC induced c-Jun N-terminal kinase (JNK) and p38 activation with peaks at 10 min; (3) azelnidipine inhibited RASMC death in a concentration-dependent manner as well as inhibited JNK and p38 activation by mechanical stretch; and (4) SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor) protected against stretch-induced RASMC death; (5) Antioxidants, diphenylene iodonium and tempol failed to inhibit stretch-induced RASMC death. On the basis of the above findings, we propose a possible mechanism where an acute rise in blood pressure increases biomechanical stress on the arterial walls, which induces RASMC death, and thus, may lead to aortic dissection. Azelnidipine may be used as a pharmacotherapeutic agent for prevention of aortic dissection independent of its blood pressure lowering effect.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Azelnidipine Inhibits Cultured Rat Aortic Smooth Muscle Cell Death Induced by Cyclic Mechanical Stretch

et al. 2014

View full text Add to dashboard Cite

show abstract

“…However, it is unknown which kinds of drugs prevents the progression of aortic aneurysm. In clinic, we sometimes administrate drugs, such as beta-blocker, angiotensin-converting enzyme-inhibitors (ACE), calcium channel blocker or statin drugs, expecting the effects of anti-inflammation in artery wall and antihypertension, though there are few strong evidences up to now [18,19]. Due to its' anti-inflammatory effects, these drugs reported to suppress aortic aneurysm progression [19,20].…”

Section: Discussionmentioning

confidence: 99%

PPAR-γ agonist attenuates inflammation in aortic aneurysm patients

Motoki

Kurobe

Hirata

et al. 2015

Gen Thorac Cardiovasc Surg

Self Cite

View full text Add to dashboard Cite

show abstract

“…Azelnidipine decreased the aortic diameter in experimental abdominal aortic aneurysms and reduced the active matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aorta [76]. In addition, azelnidipine reduced the number of macrophage antigen-3-positive cells in the periaortic adipose tissue and reduced expression levels of TNF-a, MMP-2 and MMP-9 within the aortic wall, resulting in a decrease of abdominal aortic aneurysm formation in mouse model [77]. Azelnidipine treatment significantly reduced cardiac damage and inflammatory markers, including circulating levels of TNF-a, IFN-g and TGF-b as wells as troponin-1, creatinine kinase-MB, creatinine kinase-NAC, uric acid, lactate dehydrogenase and alkaline phosphatase in a DM rat model [15].…”

Section: Azelnidipine Treatment In Patients With Essential Hypertensionmentioning

confidence: 99%

Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Shimada

Miyauchi

Daida

2014

Expert Review of Cardiovascular Therapy

View full text Add to dashboard Cite

Azelnidipine is a unique dihydropyridine calcium channel blocker with selectivity for L-type calcium channels that has been launched for the treatment of hypertension. Azelnidipine exhibits long-acting blood pressure-lowering effects without increasing heart rate. High blood pressure is associated with many metabolic disorders, including glucose intolerance and insulin resistance. Antihypertensive medications that interfere with various steps in the renin-angiotensin system improve glucose tolerance and insulin resistance; however, the effects of calcium channel blockers on glucose metabolism and insulin resistance remain controversial. Recent studies have demonstrated that azelnidipine could improve insulin resistance and glucose tolerance by potentially inhibiting sympathetic nerve activity. In addition, azelnidipine exhibits anti-inflammatory and anti-oxidative effects, suggesting that it is a beneficial antihypertensive agent with anti-atherogenic and cardioprotective effects for the treatment of not only hypertensive patients with glucose intolerance, but also those with metabolic disorders.

show abstract

Azelnidipine suppresses the progression of aortic aneurysm in wild mice model through anti-inflammatory effects

Abstract: This study demonstrates that combined treatment with angiotensin II and β-aminopropionitrile induces degenerative AAs in wild-type mice, and azelnidipine prevents aneurysm progression via its anti-inflammatory effect.

Cited by 25 publications

References 37 publications

Azelnidipine Inhibits Cultured Rat Aortic Smooth Muscle Cell Death Induced by Cyclic Mechanical Stretch

Azelnidipine Inhibits Cultured Rat Aortic Smooth Muscle Cell Death Induced by Cyclic Mechanical Stretch

PPAR-γ agonist attenuates inflammation in aortic aneurysm patients

Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders

Contact Info

Product

Resources

About