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Biomedical subjects

Alan H Matsumoto

Publications and source records attributed to Alan H Matsumoto.

At least 19 recordsLinked to original sources
PubMed2006

Direct evidence for a crucial role of the arterial wall in control of atherosclerosis susceptibility.

BACKGROUND: Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in atherosclerosis susceptibility. We sought to determine whether the difference in atherosclerosis susceptibility resides at the level of arterial walls. METHODS AND RESULTS: Thoracic aortic segments from 8-week-old female B6 and C3H apolipoprotein E-deficient mice were transplanted into the infrarenal aorta of 10-week-old female F1 mice. After transplantation, recipients were maintained on a chow diet for 16 weeks. The donor aortic segments of B6 mice developed significantly larger atherosclerotic lesions than those of C3H (44,983+/-11,702 versus 5600+/-4885 microm2 per section; P=0.011). Expression of vascular cell adhesion molecule (VCAM)-1 by endothelial cells was examined both in vitro and in vivo. B6 mice expressed significantly more VCAM-1 than their C3H counterparts. Sequence analysis of VCAM-1 cDNA revealed a nucleotide difference in the coding region that resulted in substitution of an amino acid in the protein product. CONCLUSIONS: These data provide direct proof that factors operating in the vessel wall, particularly endothelial cells, can serve as atherosclerosis modifiers and suggest a possibility for the contribution of VCAM-1 to atherosclerosis susceptibility.

Animals↗
PubMed2006

Paradoxical increase in LDL oxidation by endothelial cells from an atherosclerosis-resistant mouse strain.

Oxidative modification of LDL accumulated in the subendothelial space is a critical step in atherogenesis. Mouse strains C57BL/6 (B6) and BALB/c differ markedly in atherosclerosis susceptibility. We sought to determine whether variation of endothelial cells in the capacity to oxidize LDL or in response to minimally modified LDL (MM-LDL) constitutes a genetic component in atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid-reactive substance (TBARS) production. Responses to MM-LDL were evaluated by examining induction of monocyte chemotactic protein-1, macrophage-colony stimulating factor, and vascular cell adhesion molecule-1. Both strains exhibited comparable endothelial responses to MM-LDL, whereas BALB/c mice had an increased rate of oxidizing LDL compared with B6 mice. To examine whether endothelial nitric oxide synthase (eNOS) contributed to the difference in LDL oxidation, cells were incubated with native LDL in the presence or absence of N(Omega)-nitro-l-arginine methyl ester (l-NAME), a specific NOS inhibitor. Although l-NAME significantly inhibited endothelial cell-mediated LDL oxidation, it failed to abolish the difference between the strains. In contrast, Baicalein, a specific 12/15 lipoxygenase inhibitor, abolished the difference in LDL oxidation. Thus, the paradoxical increase in LDL oxidation by endothelial cells is attributable to higher oxidant activity of 12/15-lipoxygenase in BALB/c mice and endothelial cells appear unlikely to be a source of the resistance to atherosclerosis.

Animals↗
PubMed2006

Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice.

LDL receptor-deficient (LDLR(-/-)) mice exhibit mild hyperlipidemia on a chow diet but develop severe hyperlipidemia on a high fat diet. In this study, we investigated neointimal formation after removal of the endothelium when LDLR(-/-) mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. At 10 weeks of age, female mice underwent endothelial denudation of the left common carotid artery. Two weeks after injury, neointimal formation was barely detectable in the injured vessel when mice developed mild hyperlipidemia on the chow diet. In contrast, neointimal lesions were obvious when mice developed severe hyperlipidemia on the Western diet. Immunohistochemical and histological analyses demonstrated the presence of macrophage foam cells and smooth muscle cells in neointimal lesions. The injured artery also exhibited a significant increase in medial area on the Western diet. Plasma levels of MCP-1 and soluble VCAM-1 were significantly elevated by feeding of the Western diet. These data indicate that hyperlipidemia aggravates neointimal growth in LDLR(-/-) mice by promoting foam cell formation and inflammation.

Animal Feed↗
PubMed2006

Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice.

Dyslipidemia and hyperglycemia are integral components of the metabolic perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE(-/-)) mice develop severe hyperlipidemia and significant hyperglycemia when fed a western diet containing 21% fat (w/w), 0.15% cholesterol and 19.5% casein. Using an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE(-/-) mice, we performed quantitative trait locus (QTL) analysis to identify loci contributing to hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured after being fed the western diet for 12 weeks. QTL analysis revealed one significant QTL, named Bglu3 [95.8 cM, logarithm of odds ratio (OR)(LOD) 4.1], on chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal 1 that had a major influence on plasma SAP levels and body weight. Significant correlations between plasma glucose, SAP and body weight were observed in F2 mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE(-/-) mice and suggest a probability for the Sap gene to be a positional candidate of Bglu3.

Animals↗
PubMed2006

Deficiency of inducible NO synthase reduces advanced but not early atherosclerosis in apolipoprotein E-deficient mice.

The inducible nitric oxide synthase (iNOS) is abundantly expressed by smooth muscle cells and macrophages in atherosclerotic lesions. Apolipoprotein E-deficient (apoE(-/-)) mice develop early and advanced atherosclerotic lesions. The role of iNOS in both early and advanced atherosclerotic formation was determined in apoE(-/-) mice. Mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. At 12 weeks of age on chow diet, iNOS(-/-)/apoE(-/-) mice developed comparable sizes of early atherosclerotic lesions in the aortic root as did iNOS(+/+)/apoE(-/-) mice (30,993+/-4746 vs. 26,648+/-6815 microm(2)/section; P=0.608). After being fed the Western diet for 12 weeks, iNOS(-/-)/apoE(-/-) mice developed significantly smaller advanced lesions than iNOS(+/+)/apoE(-/-) mice (458,734+/-14,942 vs. 519,570+/-22,098 microm(2)/section; P=0.029). This reduction in lesion formation could not be explained by differences in plasma lipid levels. To examine whether iNOS contributed to LDL oxidation, smooth muscle cells were isolated from the aorta, activated with TNF-alpha, and then incubated with native LDL in the absence or presence of N-Omega-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor. L-NAME significantly inhibited LDL oxidation by smooth muscle cells from iNOS(+/+)/apoE(-/-) mice (P=0.048), but it had no effect on LDL oxidation by cells from iNOS(-/-)/apoE(-/-) mice. iNOS(-/-)/apoE(-/-) mice had a significantly lower plasma lipoperoxide level on the Western diet (2.74+/-0.23 vs. 3.89+/-0.41 microM MDA; P=0.021) but not on chow diet (1.02+/-0.07 vs. 1.51+/-0.29 microM MDA; P=0.11). Thus, the absence of iNOS-mediated LDL oxidation may contribute to the reduction in advanced lesion formation of iNOS(-/-)/apoE(-/-) mice.

Animals↗
PubMed2006

Differential response of vascular smooth muscle cells to oxidized LDL in mouse strains with different atherosclerosis susceptibility.

Oxidized low-density lipoprotein (LDL) has numerous atherogenic properties, including induction of inflammatory genes, and vascular smooth muscle cells (VSMC) are involved in the development of atherosclerosis. In this study, we examined whether variations of VSMC in the capacity to oxidize LDL or in response to minimally modified LDL (MM-LDL) constitute a genetic component in atherosclerosis. VSMC were isolated from the aorta of two inbred mouse strains C57BL/6J (B6) and C3H, which differ markedly in susceptibility to atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid-reactive substance (TBARS) production. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and an oxidant stress gene, heme oxygenase-1 (HO-1). VSMC from the two strains exhibited a comparable ability to transform native LDL to oxidized LDL, whereas their response to MM-LDL differed markedly. MM-LDL resulted in dramatic induction of MCP-1, VCAM-1, and HO-1 mRNAs in the cells from B6 mice but exerted little effect in cells from C3H mice. MCP-1 and soluble VCAM-1 protein levels in conditioned media were measured by ELISA. B6 cells produced significantly more MCP-1 and VCAM-1 proteins in response to MM-LDL than C3H cells. These data suggest that variation in the response of VSMC to oxidized LDL may contribute to the difference between B6 and C3H mice in atherosclerosis susceptibility.

Animals↗
PubMed2006

Thoracic aortic endografting is the treatment of choice for elderly patients with thoracic aortic disease.

OBJECTIVE: To assess the effect of age on outcomes following thoracic aortic endografting. SUMMARY BACKGROUND DATA: Endograft therapy for thoracic aortic disease is rapidly evolving. This therapy is less invasive, and elderly patients with significant medical comorbidities are more frequently referred for endografting. We hypothesized that elderly patients over the age of 75 have worse outcomes after thoracic endografting than patients under the age of 75. METHODS: We retrospectively reviewed the charts of the first 42 patients who underwent endografting for thoracic aortic pathology. Charts were reviewed for demographics, comorbid conditions, perioperative complications and death, endoleaks, and results at 3, 6, and 12 months. Preexisting medical conditions were also evaluated to determine if any patient characteristics were associated with adverse outcomes. Perioperative morbidity included cardiac, pulmonary, renal, hemorrhagic, and neurologic (stroke and spinal cord injury) complications. RESULTS: Twenty-four patients were under the age of 75, and 18 patients were 75 or older. Baseline demographics and comorbidities were similar between the 2 groups. There were no differences in operative time, length of stay, perioperative mortality, or the incidence of significant complications between the 2 age groups. Gender, however, was associated with a statistically significant difference between the occurrence of complications, with more women experiencing complications than men (P = 0.026, relative risk = 2.36). One patient (age >75 years) in the entire cohort of 42 (2.4%) suffered a spinal cord injury. At 3 months, endoleaks were more common in the older age group (P = 0.059). CONCLUSION: Endograft therapy for thoracic aortic disease can be performed safely in elderly patients with no significant increase in perioperative morbidity or mortality compared with younger patients. Female gender is associated with a higher likelihood of perioperative complications, regardless of age. The overall incidence of spinal cord injury is very low. Endograft therapy, when anatomically possible, is the treatment of choice for thoracic aortic disease in elderly patients.

Adult↗
PubMed2005

Quantitative trait locus analysis of atherosclerosis in an intercross between C57BL/6 and C3H mice carrying the mutant apolipoprotein E gene.

Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) differ significantly in atherosclerosis susceptibility and plasma lipid levels on the apolipoprotein E-deficient (apoE-/-) background when fed a Western diet. To determine genetic factors contributing to the variations in these phenotypes, we performed quantitative trait locus (QTL) analysis using an intercross between the two strains carrying the apoE-/- gene. Atherosclerotic lesions at the aortic root and plasma lipid levels of 234 female F2 mice were analyzed after being fed a Western diet for 12 weeks. QTL analysis revealed one significant QTL, named Ath22 (42 cM, LOD 4.1), on chromosome 9 and a suggestive QTL near D11mit236 (20 cM, LOD 2.4) on chromosome 11 that influenced atherosclerotic lesion size. One significant QTL on distal chromosome 1, which accounted for major variations in plasma LDL/VLDL cholesterol and triglyceride levels, coincided with a QTL having strong effects on body weight. Plasma LDL/VLDL cholesterol or triglyceride levels of F2 mice were significantly correlated with body weight, but they were not correlated with atherosclerotic lesion sizes. These data indicate that atherosclerosis susceptibility and plasma cholesterol levels are controlled by separate genetic factors in the B6 and C3H mouse model and that genetic linkages exist between body weight and lipoprotein metabolism.

Animals↗
PubMed2005

Magnetic resonance urography for the assessment of potential renal donors: comparison of the RARE technique with a low-dose gadolinium-enhanced magnetic resonance urography technique in the absence of pharmacological and mechanical intervention.

The aim of this study was to determine whether magnetic resonance urography without pharmacological (diuretic) stimulation and mechanical compression allows conclusive evaluation of the urinary system in potential renal donors. In 28 consecutive patients magnetic resonance urography (MRU) was performed on a 1.5-T system. Two techniques, rapid acquisition with relaxation enhancement (RARE) and a gadolinium (Gd)-enhanced 3D fast low angle shot (FLASH) sequence were compared in the absence of adjunctive measures. Two reviewers assessed image quality, presence of artifacts and completeness of visualization of the collecting systems and ureters. Among the 53 MR urograms, there was no difference in image quality and presence of artifacts between RARE and Gd-MRU. Despite high image quality, visualization of the urinary collecting system was insufficient. Continuous visualization from the collecting system to the distal ureter was demonstrated bilaterally in only 14% of the RARE and 26% of Gd-enhanced MR urograms, respectively. Overall, Gd-enhanced MRU was superior to the RARE technique in displaying the segments of the urinary collecting system, but this difference was not found to be statistically significant. Neither the RARE technique nor the gadolinium-enhanced MRU technique is accurate enough to allow the evaluation of the collecting system and ureters in potential renal donors in the absence of pharmacological intervention and compression.

Adult↗
PubMed2005

Circulating adhesion molecules in apoE-deficient mouse strains with different atherosclerosis susceptibility.

Recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in development of atherosclerosis. Apolipoprotein E-deficient (apoE(-/-)) mice have spontaneous hyperlipidemia and develop all phases of atherosclerotic lesions. We sought to examine plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and sP-selectin in two apoE(-/-) strains C57BL/6 (B6) and BALB/c with early or advanced lesions. Mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. On either diet, BALB/c.apoE(-/-) mice developed much smaller atherosclerotic lesions and displayed significantly lower levels of sVCAM-1 and sP-selectin than B6.apoE(-/-) mice. The Western diet significantly elevated sVCAM-1 levels in both strains and sP-selectin levels in B6.apoE(-/-) mice. BALB/c.apoE(-/-) mice exhibited 2-fold higher HDL cholesterol levels on the chow diet and 15-fold higher HDL levels on the Western diet than B6.apoE(-/-) mice, although the two strains had comparable levels of total cholesterol and triglyceride. Thus, increased atherosclerosis is accompanied by increases in circulating VCAM-1 and P-selectin levels in the two apoE(-/-) mouse strains, and the high HDL level may protect against atherosclerosis by inhibiting the expression of adhesion molecules in BALB/c.apoE(-/-) mice.

Animals↗
PubMed2005

Subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) for subintimal recanalization to treat chronic critical limb ischemia.

PURPOSE: To describe the technique of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success for the performance of subintimal recanalization when there is failure to reenter the distal true lumen or when there is a limited segment of patent distal target artery available for reentry. MATERIALS AND METHODS: Subintimal recanalization was attempted in an antegrade direction in all patients. If reentry into the distal true lumen was unsuccessful or a short segment of target artery was present, retrograde access was obtained in the distal target artery (popliteal, anterior tibial/dorsalis pedis, or posterior tibial) and a retrograde subintimal channel was created. A guide wire was used to connect the retrograde and antegrade subintimal channels simultaneously to create a "flossing" guide wire. The subintimal tract was dilated with balloon angioplasty with or without stent implantation. Limb salvage, amputation-free survival, and survival rates over time were determined. RESULTS: The SAFARI technique resulted in successful subintimal recanalization creating straight-line flow to the foot in all 21 limbs in 20 patients in which the technique was attempted. Antegrade-retrograde access was performed with the femoral artery and the following vessels: popliteal, n = 11; anterior tibial/dorsalis pedis, n = 10; and posterior tibial, n = 2 (two limbs involved multiple accesses). All procedures were successful. The limb salvage rate with SAFARI was 90% (95% CI, 74%-100%) at 6 months. CONCLUSIONS: The SAFARI technique can be useful for completing subintimal recanalization when there is failure to reenter the distal true lumen from an antegrade approach or when there is limited distal target artery available for reentry. The SAFARI technique improves technical success in the performance of subintimal recanalization. Limb salvage rates are comparable to those with antegrade subintimal recanalization.

Aged↗
PubMed2004

Neointimal formation in two apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility.

C57BL/6 (B6) and C3H/HeJ (C3H) are two commonly used mouse strains that differ markedly in atherosclerosis susceptibility. In this study, we determined plaque formation after removal of the endothelium in the two strains carrying the mutant apolipoprotein E gene (apoE(-/-)). At 10 weeks of age, male B6.apoE(-/-) and C3H.apoE(-/-) mice underwent endothelial denudation of the left common carotid artery. Two weeks after injury, B6.apoE(-/-) mice developed significantly larger neointimal lesions in the vessel than their C3H.apoE(-/-) counterparts, although they had comparable plasma cholesterol levels on a chow diet. Feeding of a Western diet aggravated lesion formation in both strains, but the increase was more dramatic in B6.apoE(-/-) mice than in C3H.apoE(-/-) mice. Immunohistochemical and histological analyses demonstrated the presence of macrophage foam cells in neointimal lesions. We then compared neointimal growth in F1 mice reconstituted with bone marrow from B6.apoE(-/-) and C3H.apoE(-/-) mice. No significant lesions were observed 2 weeks after endothelial denudation in the mice reconstituted with bone marrow from either donor. Thus, these data indicate that foam cell formation contributes to neointimal growth in the hyperlipidemic apoE(-/-) model and that neither endothelial cells nor blood cells alone explain the dramatic difference between B6 and C3H mice in plaque formation.

Animal Feed↗
PubMed2004

Pancreatic pseudoaneurysm in a child with hereditary pancreatitis: diagnosis with multidetector CT angiography.

Pseudoaneurysm formation is a serious vascular complication of pancreatitis. It most commonly affects splenic and gastroduodenal arteries. We report a rare case of superior mesenteric artery pseudoaneurysm in a child with hereditary pancreatitis. Multidetector CT angiography allowed the comprehensive assessment of the aneurysm and allowed accurate surgical planning obviating the need for catheter angiography.

Aneurysm, False↗
PubMed2004

Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility.

LDL deposition in the subendothelium of arterial walls is the initial event in the development of atherosclerosis. The deposited LDL undergoes oxidative modification by arterial wall cells to become oxidized LDL and consequently contributes to atherosclerotic formation. Using mouse strains C57BL/6J (B6) and C3H/HeJ (C3H), which differ markedly in susceptibility to atherosclerosis, we determined whether variation in subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins constitutes a genetic component in atherosclerosis. Lipoprotein retention was quantitated by Western blot analysis to detect the presence of apoB in aortic walls before foam cells developed. In both dietary and apoE-deficient models, B6 mice exhibited up to a 2-fold increase of apoB in the aortic wall compared with C3H mice. This increase could not be attributed to differences in plasma lipid levels of the two strains. In vitro, endothelial cells from C3H mice took up more acetylated and oxidized LDL but not native LDL and converted more native LDL to oxidized LDL than did endothelial cells from B6 mice. C3H mice expressed more scavenger receptor A in their aortic wall than B6 mice. Thus, variation in the subendothelial retention of apoB-containing lipoproteins cannot explain the dramatic difference in atherosclerosis susceptibility between B6 and C3H mice, and endothelial cells may play a role in alleviating lipid accumulation in arterial walls.

Acetylation↗