Collagen alteration in vascular remodeling by hemodynamic factors

Ishikawa, Yukio; Asuwa, Noriko; Ishii, Toshiharu; Ito, Kinji; Akasaka, Yoshikiyo; Masuda, Tomoaki; Zhang, Lijun; Kiguchi, Hideko

doi:10.1007/s004280000200

Cited by 43 publications

(38 citation statements)

References 31 publications

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“…Therefore, we investigated the regulation of cerebrovascular MMPs that can degrade collagen (MMP-1) and gelatin (MMP-2 and -9). Increased extracellular matrix protein synthesis, diminished MMP activity, and/or increased TIMP activity all could contribute to matrix accumulation, which is a late event in the vascular remodeling process (36). Interestingly, recent studies demonstrated that MMP activation also contributes to vascular smooth muscle cell growth and migration as well as increased collagen synthesis via several mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes Causes Remodeling of Cerebrovasculature via Differential Regulation of Matrix Metalloproteinases and Collagen Synthesis

et al. 2005

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The risk of cerebrovascular disease is four-to sixfold higher in patients with diabetes. Vascular remodeling, characterized by extracellular matrix deposition and an increased media-to-lumen ratio, occurs in diabetes and contributes to the development of complications. However, diabetes-induced changes in the cerebrovascular structure remain unknown. Endothelin-1 (ET-1), a potent vasoconstrictor with profibrotic properties, is chronically elevated in diabetes. To determine diabetesmediated changes in the cerebrovasculature and the role of ET-1 in this process, type 2 diabetic GotoKakizaki (GK) rats were administered an ET A receptor antagonist for 4 weeks. Middle cerebral arteries were harvested and studies were performed to determine vascular structure. Tissue and plasma ET-1 levels were increased in GK rats compared with controls. Significant medial hypertrophy and collagen deposition resulted in an increased wall-to-lumen ratio in diabetic rats that was reduced by ET A receptor antagonism. Vascular matrix metalloproteinase (MMP)-2 activity was higher, but MMP-1 levels were significantly reduced in GK rats, and MMP levels were restored to control levels by ET A receptor antagonism. We conclude that ET-1 promotes cerebrovascular remodeling in type 2 diabetes through differential regulation of MMPs. Augmented cerebrovascular remodeling may contribute to an increased risk of stroke in diabetes, and ET A receptor antagonism may offer a novel therapeutic target. Diabetes 54:2638 -2644, 2005 T ype 2 diabetes, a disease that affects more than 17 million Americans, holds a two-to sixfold increased risk for cerebrovascular disease and stroke (1,2), and 70% of patients with a recent stroke have overt diabetes or pre-diabetes characterized by impaired fasting glucose or impaired glucose tolerance (3). However, the underlying basis of this predisposition remains unclear. Diabetic vascular complications are associated with remodeling of the vessel wall in the retinal, renal, and mesenteric circulations. However, diabetesinduced structural changes in the cerebral microvessels are unknown.The endothelium is an early target in diabetes, and dysfunction of vascular endothelial cells has a role in the diabetic vascular disease process (4). For example, the release of vasodilator and antiproliferative mediators such as nitric oxide and prostaglandin-I 2 is decreased, whereas production of endothelin-1 (ET-1) is increased (5). A significant correlation has been observed between plasma ET-1 levels and diabetes complications. In addition to being vasoconstrictive, ET-1 is also mitogenic. In streptozotocin-induced diabetes, nonselective ET receptor antagonism prevents extracellular matrix deposition in the retina as well as in the mesenteric arteries, providing evidence for a causal relationship (6,7). Nonselective blockade of ET receptors also prevents increased myogenic tone of cerebral vessels in diabetes (8), but the effect on vascular structure and the underlying mechanisms remain to be identified.The matrix metalloproteinases ...

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Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes Causes Remodeling of Cerebrovasculature via Differential Regulation of Matrix Metalloproteinases and Collagen Synthesis

et al. 2005

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“…With increased flow, an upregulation of ECM genes, including collagen genes in the pulmonary artery [37], an increase of spiraled collagen in coronary arteries [38] and in collagen turnover [39] has been reported. In vitro, the gene expression of TGFβ1, a cytokine well-known to enhance collagen deposition, was increased in vascular smooth muscle cells exposed to shear stress [40].…”

Section: Discussionmentioning

confidence: 99%

High-Flow-Induced Arterial Remodeling in Rats with Different Susceptibilities to Cerebral Aneurysms

Coutard

Osborne-Pellegrin²,

Fontaine³

et al. 2006

J Vasc Res

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Background: The higher incidence of cerebral aneurysms (CAs) induced by enhanced arterial blood flow in Long Evans (LE) compared to Brown Norway (BN) rats suggests that intrinsic differences in high-flow arterial remodeling may be involved in determining CA susceptibility. Some aspects of this remodeling were compared in LE and BN rats after creation of an abdominal aortocaval fistula (ACF). Methods and Results: At 4 days with ACF, aortic luminal cross-sectional area (LCSA) determined by morphometry was increased by 20% in LE but not in BN rats. mRNA levels, determined by RT-PCR, were higher in LE than in BN rats for collagen α1(I), collagen α1(III), MMP2 and its inhibitor TIMP1 at 19 days with ACF. Nitric oxide synthase (NOS) mRNA levels were higher in LE rats at 4 days for the inducible (NOS2) isoform and at 4 and 19 days for the neuronal (NOS1) isoform. Aortic LCSA and NOS1 mRNA levels were tightly correlated and NOS inhibition prevented ACF-induced aortic remodeling in the LE rat. MMP2 and MMP7 activity, evaluated by zymography at 4 days with ACF, did not greatly differ between BN and LE. Conclusions: These data suggest that a higher intrinsic ability for high-flow-induced arterial enlargement associated with NOS gene overexpression may be a possible genetic determinant in CA susceptibility.

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“…Studies on other factors, such as hemodynamic [13] and molecular [21] factors, are expected to elucidate this issue. Shear stress, in particular, is considered to be an important factor, because it affects regional metabolism of cellular and matrix components, such as collagens, in the intima [11].…”

Section: Correlation Between the Distributions Of Dit And Those Of Atmentioning

confidence: 99%

Distributions of diffuse intimal thickening in human arteries: preferential expression in atherosclerosis-prone arteries from an early age

et al. 2002

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Diffuse intimal thickening (DIT) is a thickened intima present in human arteries before atherosclerosis develops and is considered to be related to atherogenesis. The purpose of this study was to clarify the systemic and age distributions of DIT. Coronary, cerebral, carotid, subclavian, iliac and abdominal organ arteries and the aorta were examined in 72 autopsy cases (aged 36 weeks of gestation to 30 years at death). DIT was found in the coronary arteries and aorta from 36 weeks of gestation and the first year of life, respectively. The intima/media (I/M) ratio of coronary arteries showed an age-dependent increase and was much greater than that of other muscular arteries, i.e., intracranial and extraparenchymal cerebral arteries and abdominal organ arteries. Aorta also demonstrated age-dependent as well as site-dependent increases of I/M ratio; the more distal the segments, the greater the ratio. Consequently, the abdominal aorta had the largest I/M ratio within the aorta. Other elastic arteries, i.e., carotid, subclavian and iliac arteries, showed trends similar to the distal portions of the aorta. Thus, DIT was strongly expressed from an early age in arteries that are considered to be prone to atherosclerosis. These findings suggest that the development of atherosclerosis depends at least partly on the degree of DIT.

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Collagen alteration in vascular remodeling by hemodynamic factors

Cited by 43 publications

References 31 publications

Type 2 Diabetes Causes Remodeling of Cerebrovasculature via Differential Regulation of Matrix Metalloproteinases and Collagen Synthesis

Type 2 Diabetes Causes Remodeling of Cerebrovasculature via Differential Regulation of Matrix Metalloproteinases and Collagen Synthesis

High-Flow-Induced Arterial Remodeling in Rats with Different Susceptibilities to Cerebral Aneurysms

Distributions of diffuse intimal thickening in human arteries: preferential expression in atherosclerosis-prone arteries from an early age

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