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Biomedical subjects

B E Sumpio

Publications and source records attributed to B E Sumpio.

At least 19 recordsLinked to original sources
PubMed2005

Review of prevalence and outcome of vascular disease in patients with diabetes mellitus.

OBJECTIVES: Review the literature to determine the prevalence and outcome in patients with diabetes that undergo surgery to correct carotid artery stenosis, lower extremity arterial disease, and abdominal aortic aneurysm (AAA). DESIGN AND MATERIALS: Studies were obtained from searches over the past 15 years on the National Library of Medicine's online search engine. RESULTS: The review demonstrated an equivalent prevalence of carotid artery stenosis requiring surgery in patients with diabetes, it favored no increase risk of post-CEA stroke, and it was split on perioperative morbidity and mortality risk. There was an increase prevalence of lower extremity arterial disease requiring surgery in patients with diabetes, it favored equivalent patency and limb salvage rates, and it was split on the morbidity and mortality risk. The review demonstrated a decrease in AAA prevalence among patients with diabetes, it found an increase in the morbidity risk, and equivalent mortality risk. CONCLUSIONS: Stroke, graft patency, and limb salvage rates in patients with diabetes after surgery are similar to patients without diabetes; however, their risk of complications is increased after surgery and the mortality risk may be higher after CEA.

Aortic Aneurysm, Abdominal↗
PubMed2003

An appraisal of different cardiac risk reduction strategies in vascular surgery patients.

OBJECTIVES: to summarize existing evidence regarding the benefits and the risks of all available interventional and medical means aimed at cardiac risk reduction in patients undergoing vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a critical review of all studies examining the impact of various prophylactic cardiac maneuvers on perioperative outcome following vascular surgery was performed. Overall mortality, cardiac mortality and myocardial infarction rate were used as the outcome measures. RESULTS: coronary artery bypass grafting is associated with a 60% decrease in perioperative mortality in patients undergoing vascular surgery, but in most of the cases this decrease does not outweigh the combined risk of the cardiac and the subsequent noncardiac vascular procedure. Data supporting the cardioprotective effect of percutaneous transluminal angioplasty in the perioperative setting are insufficient. beta-blockade has been shown to decrease perioperative mortality and cardiac morbidity in both high-risk (strong evidence) and low-risk (weak evidence) patients. CONCLUSIONS: coronary revascularization is rarely indicated to simply get the patient through vascular surgery and should be reserved for patients who would need it irrespective of the scheduled vascular procedure. Among all available pharmacological agents, including beta-blockers, alpha-agonists, calcium channel blockers and nitrates, only beta-blockers have been proven to reduce the cardiac risk of vascular surgery.

Cardiac Surgical Procedures↗
PubMed2003

Immunobiologic analysis of arterial tissue in Buerger's disease.

INTRODUCTION: the cause of thromboangiitis obliterans (TAO) still remains unknown. We have reported that immunologic injury associated with T lymphocytes infiltration might be the initial etiologic mechanism in TAO. The present study was undertaken to examine further the mechanism of immune injury. METHODS: arterial walls affected by TAO were obtained from eight patients with eight non-pulsatile arteries and one patent artery. Immunohistochemical and TUNEL studies were performed for phenotyping of the infiltrating cells with CD4 (helper T cell), CD8 (cytotoxic T cell), CD56 (natural killer cell), and CD68 (macrophage), for identification of cell activation with VCAM-1 and i -NOS, for the presence of cell death with TUNEL analysis, and for inflammatory cytokine detection with RT-PCR. RESULTS: the characteristic features were luminal obliteration, together with a varying degree of recanalization. T cells infiltrated mainly in thrombus, intima, and adventita. Among infiltrating cells, CD4 T cells greatly outnumbered CD8 cells. VCAM-1 and i -NOS were expressed in endothelial cells around the intima (patent segment) or vaso vasorum (occluded segment). Endothelial cells in vaso vasorum stained positive with TUNEL. Interferon-gamma mRNA was detected in two specimens. CONCLUSIONS: our results suggest that T cell mediated immune inflammation is a significant event in the development of TAO.

Adult↗
PubMed2001

Translocation of PKC isoforms in bovine aortic smooth muscle cells exposed to strain.

Our laboratory has previously reported that the exposure of smooth muscle cells (SMC) to the cyclic strain results in significant stimulation of protein kinase C (PKC) activity by translocating the enzyme from the cytosol to the particulate fraction. We now sought to examine the strain-induced translocation of individual PKC isoforms in SMC. Confluent bovine aortic SMC grown on collagen type I-coated plates were exposed to cyclic strain for up to 100 s at average 10% strain with 60 cycles/min. Immunoblotting analysis demonstrates that SMC express PKC-alpha, -beta and -zeta in both cytosolic and particulate fractions. Especially, PKC-alpha and -zeta were predominantly expressed in the cytosolic fraction. However, cyclic strain significantly (P < 0.05) increased PKC-alpha and -zeta in the particulate fraction and decreased in the cytosolic fraction. Thus, the cyclic strain-mediated stimulation of PKC activity in SMC may be due to the translocation of PKC-alpha and -zeta from the cytosolic to the particulate fraction. These results demonstrate that mechanical deformation causes rapid translocation of PKC isoforms, which may initiate a cascade of proliferation responses of SMC since NF-kappaB, which is involved in the cellular proliferation has been known to be activated by these PKC isoforms.

Animals↗
PubMed2001

Intermittent pneumatic compression devices -- physiological mechanisms of action.

There are many reports of how IPC is used effectively in the clinical setting; including the prevention of deep venous thrombosis, improvement of circulation in patients with lower extremity arterial diseases, reduction of lymphoedema, and the healing of venous ulcers. However, despite the widely accepted use of IPC, it is still unclear how IPC actually exerts its beneficial effects. The exact physiological mechanisms of action are unknown. The clinical utility of IPC and the putative mechanisms by which IPC could exert its therapeutic effect will be reviewed. The paper will examine the mechanical effects of IPC exerted on the lower extremity, and the subsequent biochemical changes in the circulation. In vitro studies of the effects of mechanical stress such as compressive strain and shear on cultured endothelial cells, and their clinical relevance to IPC will also be reviewed.

Adult↗
PubMed2001

Cyclic strain activates the pro-survival Akt protein kinase in bovine aortic smooth muscle cells.

BACKGROUND: Pulsatile pressure induced by the beating heart causes cyclic strain on arterial endothelial cells and smooth muscle cells (SMCs). This study examined whether Akt, a serine/threonine protein kinase known to promote cell survival by inhibiting apoptosis, is activated by cyclic strain in bovine aortic SMCs. METHODS: Bovine aortic SMCs were cultured on flexible-bottomed membranes and then serum-starved for 24 to 36 hours. The cells were then exposed to 150-mm Hg repetitive deformations, which created an average of 10% strain on the monolayer SMCs at a frequency of 60 cycles/minute for 0 (negative control) and 30 minutes. Platelet-derived growth factor (PDGF)--stimulated SMCs were used as positive controls. Phosphorylation of Akt was determined by means of Western blot analysis. An apoptosis assay (TUNEL) was also performed on SMCs exposed to cyclic strain. RESULTS: Akt phosphorylation was significantly increased over that of the negative control after 30 minutes of cyclic strain and in the PDGF group. Cyclic strain did not increase the prevalence of apoptosis in SMCs over the control. CONCLUSIONS: Cyclic strain activated the pro-survival Akt kinase. The pro-survival function was supported by the fact that cyclic strain did not increase apoptosis in bovine aortic SMCs. This experiment suggests that cyclic strain may induce arterial wall thickening by tipping the balance toward arterial SMC proliferation through the inhibition of apoptosis.

Animals↗
PubMed2001

The C-terminal domain of thrombospondin-1 induces vascular smooth muscle cell chemotaxis.

OBJECTIVE: Thrombospondin-1 (TSP-1), an acute-phase reactant implicated in vascular disease, is a 420-kd multifunctional glycoprotein chemotactic for vascular smooth muscle cells (VSMCs). TSP-1 has six domains of repeating homologous amino acid sequences: N-terminal, procollagen homology, type 1 repeat, type 2 repeat, type 3 repeat/RGD (T3), and C-terminal (COOH). The purpose of this experiment was to determine which domains of TSP-1 induce VSMC chemotaxis. METHODS: A modified Boyden Chamber chemotaxis assay was used to assess VSMC migration. Serum-free medium, TSP-1, or each of the fusion proteins (10 and 20 microg/mL) synthesized for the different domains were placed in the bottom wells. Quiescent bovine aortic VSMCs (50,000) were placed in the top wells. After 4 hours at 37 degrees C, migrated VSMCs were recorded as cells per five fields (400x) and analyzed with the paired t test. To verify the fusion protein data, we performed chemotaxis assays with antibodies to each of the domains (25 microg/mL) combined with TSP-1 (20 microg/mL) in the bottom wells and VSMCs in the top wells. RESULTS: The COOH domain significantly stimulated VSMC chemotaxis (P = <.001). To a lesser extent, the N-terminal and T3 domains also induced chemotaxis (P <.05). However, only the anti-COOH antibody (C6.7) and the anti-integrin-associated protein portion of COOH antibody (D4.6) significantly inhibited TSP-1-induced VSMC chemotaxis (by 85% and 92%, respectively). CONCLUSIONS: These results implicate the COOH domain as the portion of the TSP-1 molecule primarily responsible for VSMC chemotaxis. This experiment suggests that future strategies in the prevention of VSMC migration, an initial step in the development of vascular lesions, may involve selective inhibition of the COOH domain of TSP-1.

Animals↗
PubMed2001

Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells.

Rhythmic strain stimulates Caco-2 proliferation. We asked whether mitogen-activated protein kinase (MAPK) activation mediates strain mitogenicity and characterized upstream signals regulating MAPK. Caco-2 cells were subjected to strain on collagen I-precoated membranes or antibodies to integrin subunits. Twenty-four hours of cyclic strain increased cell numbers compared with static conditions. MAPK-extracellular signal-regulated kinase (ERK) kinase inhibition (20 microM PD-98059) blocked strain mitogenicity. p38 Inhibition (10 microM SB-202190) did not. Strain rapidly and time-dependently activated focal adhesion kinase (FAK), paxillin, ERK1 and 2, and p38 on collagen. c-Jun NH(2)-terminal kinase (JNK)1 and 2 exhibited delayed activation. Similar activation occurred when Caco-2 cells were subjected to strain on a substrate of functional antibody to the alpha2-, alpha3-, alpha6-, or beta1-integrin subunits but not on a substrate of functional antibody to the alpha5-subunit. FAK inhibition by FAK397 transfection blocked ERK2 and JNK1 activation by in vitro kinase assays, but pharmacological protein kinase C inhibition did not block ERK1 or 2 activation by strain. Strain-induced ERK signals mediate strain's mitogenic effects and may require integrins and FAK activation.

Caco-2 Cells↗
PubMed2001

Role of p38 MAP kinase in endothelial cell alignment induced by fluid shear stress.

The p38/mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MAPKAP kinase 2)/heat shock protein (HSP)25/27 pathway is thought to play a critical role in actin dynamics. In the present study, we examined whether p38 was involved in the morphological changes seen in endothelial cells (EC) exposed to shear stress. Cultured bovine aortic EC were subjected to 14 dyn/cm(2) laminar steady shear stress. Peak activation of p38, MAPKAP kinase 2, and HSP25 were sixfold at 5 min, sixfold at 5 min, and threefold at 30 min compared with static control, respectively. SB-203580 (1 microM), a specific inhibitor of p38, abolished the activation of MAPKAP kinase 2 and HSP25 as well as EC elongation and alignment in the direction of flow elicited by shear stress. The mean orientation angle of cells subjected to shear without SB-203580, with SB-203580, or static control were 17, 50, and 43 degrees, respectively (P < 0. 05). EC transfected with the dominant negative mutant of p38-alpha aligned randomly with no stress fiber formation despite exposure to shear stress. These data suggests that the pathway of p38/MAPKAP kinase 2/HSP25/27 is activated in response to shear stress, and this pathway plays an important role in morphological changes induced by shear stress.

Animals↗
PubMed2001

The integrin-mediated cyclic strain-induced signaling pathway in vascular endothelial cells.

The irregular distribution of plaque in the vasculature results from the interaction of local hemodynamic forces with the vessel wall. One well-characterized force is cyclic circumferential strain, the repetitive pulsatile pressure distention on the arterial wall. This review summarizes current research, which has aimed to elicit the signal transduction pathway by which cyclic strain elicits functional and structural responses in endothelial cells; specifically, it summarizes the signaling pathway that begins with the reorganization of integrins. One method by which these extracellular matrix receptors affect signal transduction is through their ability to initiate the process of phosphorylation on tyrosine residues of cytoplasmic protein kinases, including focal adhesion kinase. The strain-induced pathway appears to also involve ras and the mitogen-activated protein kinase family of enzymes, and preliminary data suggests a role for src as well. Ultimately, it is the regulation of gene expression through the modulation of transcription factors that allows endothelial cells to respond to changes in local hemodynamics.

Blood Pressure↗
PubMed2001

Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth muscle cells.

OBJECTIVE: Accumulating evidence links the release of vascular endothelial growth factor (VEGF) by vascular smooth muscle cells (VSMC) to normal endothelial cell (EC) function, repair and maintenance. Using an in vitro model we investigate the role of cyclic stretch on both the release of VEGF by VSMC and the phosphorylation of a VEGF receptor on EC. METHODS: Bovine VSMC and EC were exposed to 10% cyclic strain for 4 hours. VEGF mRNA steady-state levels of VSMC were analysed by northern blot hybridisation. The presence of secreted VEGF from VSMC was determined by assaying the migration of EC. VEGF receptor phosphorylation on stretched EC was assayed by immunoblotting. RESULTS: The steady-state level of VEGF mRNA in stretched VSMC increased 3.3 (+/- 0.6) fold above that of unstretched VSMC (p < 0.005). Migration of EC was stimulated 8.3 (+/- 1.1) and 14.6 (+/- 1.3) fold by media from unstretched and stretched VSMC respectively, demonstrating a 1.8 fold increase due to stretch alone (p < 0.05). Cyclic stretch resulted in phosphorylation of the VEGF receptor KDR. CONCLUSION: Exposure of VSMC to physiological levels of stretch induces a biologically significant increase in VEGF secretion and may provide an arterial stimulus for maintenance of steady state levels of VEGF essential for EC survival.

Animals↗
PubMed2000

Foot ulcers.

The role of the primary care physician in the evaluation, diagnosis, and management of pedal wounds is critical (Table 2). Patient education is essential for the reduction of risk factors and for the early recognition of foot complications. Careful assessment of vascular disease (leading to bypass surgery when indicated), evaluation and management of biomechanical abnormalities, and aggressive treatment of any infections are also required. Optimal management can reduce the number of major amputations, prevent infection, decrease the probability of ulceration, maintain skin integrity, and improve function. The multidisciplinary approach will provide a comprehensive treatment protocol that will increase the long-term viability of the foot.

Biomechanical Phenomena↗
PubMed2000

Mitogen-activated protein phosphorylation in endothelial cells exposed to hyperosmolar conditions.

The effect of hyperosmolarity on the induction of the mitogen-activated protein kinases (MAPK) was studied in bovine aortic endothelial cell (EC). Different types of agents were used to differentiate the effects of osmolarity from other variables. Hypertonic treatment with physiologically relevant levels of NaCl (350 mOsm/kg H(2)O) significantly increased the level of expression of p38 within 2 min, and ERK-1/2 and JNK after 10 min. The inductions peaked between 30 and 60 min and returned to baseline levels within 2 h. A similar pattern of induction occurred with ionic contrast agent. p38 induction by glucose and mannitol showed a similar pattern, although the level of ERK-1/2 phosphorylation was not as robust, and JNK was not induced by glucose. Urea did not affect the level of induction of the MAPK isoforms. It is concluded that MAPK plays an important role in hyperosmolality-induced signal transduction. Different osmotic agents induce MAPK expression differently. No MAPK induction with urea implies that cell shrinkage may be an important component of hyperosmolality-induced MAPK phosphorylation.

Animals↗
PubMed2000

Effects of increased ambient pressure on colon cancer cell adhesion.

Forces such as strain modulate intestinal epithelial biology. Shear and pressure influence other cells. The effects of pressure on human colon cancer cells are poorly understood. Increasing ambient pressure for 30 min by 15 mm Hg over atmospheric stimulated adhesion to matrix proteins of four human colon cancer cell lines and primary cells from three human colon cancers, but not bovine aortic smooth-muscle cells. This effect was energy dependent and cation dependent (blocked by azide and chelation), accompanied by tyrosine phosphorylation of intracellular proteins including focal adhesion kinase, and blocked by tyrosine kinase inhibition (genistein, tyrphostin, and erbstatin) and a functional antibody to the beta1 integrin subunit. Although pressure stimulated adhesion even in a balanced salt solution, baseline and pressure-stimulated adhesion were each substantially diminished in the absence of serum. These data suggest that relatively low levels of increased pressure may stimulate malignant colonocyte adhesion by a cation-dependent beta1-integrin-mediated mechanism, perhaps via focal adhesion kinase-related tyrosine phosphorylation. In addition to elucidating another aspect of physical force regulation of colonocyte biology, these findings may be relevant to the effects of increased pressure engendered by colonic peristalsis, surgical manipulation, or laparoscopic surgery on colon cancer cell adhesion.

Animals↗
PubMed2000

Role of caveolin in hemodynamic force-mediated endothelial changes.

BACKGROUND: Caveolin has been shown to play an important role in signal transduction and nitric oxide synthase production. The purpose of this study was to investigate whether caveolin was tyrosine phosphorylated or activated by shear stress or cyclic strain in bovine aortic endothelial cells (BAECs). MATERIALS AND METHODS: BAECs were subjected to an average of 10% strain at a rate of 60 cycles/min or a laminar shear stress of 10 dyn/cm(2) for up to 4 h. Immunoblotting with anticaveolin antibody was performed to assess activation of caveolin. Coimmunoprecipitation of anticaveolin antibody with anti-tyrosine phosphorylation antibody was performed to detect the tyrosine phosphorylation of caveolin. RESULTS: Neither cyclic strain nor shear stress at physiologic levels altered the level of caveolin protein. Tyrosine phosphorylation of caveolin could not be observed at any time under either cyclic strain or shear stress condition. CONCLUSION: Although hemodynamic forces alter nitric oxide synthase production and activate signal transduction, caveolin levels or activity is not altered in endothelial cells exposed to shear stress or cyclic strain.

Animals↗
PubMed2000

Homocysteine stimulates MAP kinase in bovine aortic smooth muscle cells.

BACKGROUND: Hyperhomocysteinemia is recognized as a risk factor for atherosclerotic disease. However, the mechanism of homocysteine effects on smooth muscle cell proliferation, which is a hallmark of atherosclerosis, is unknown. The object of this study was to test the effects of homocysteine on smooth muscle cell proliferation, and to examine the mitogen-activated protein (MAP) kinases, extracellular signal-regulated protein kinase 1 and 2, that are known to be involved in cell proliferation. METHODS: For the proliferation study, bovine aortic smooth muscle cells (BASMC, 10, 000/well) were allowed to grow for 2 days before 2 mmol/L D,L -homocysteine was added for 2, 4, 6, and 8 days to simulate the clinical hyperhomocysteinemic condition. For the MAP kinase study, quiescent BASMC were exposed to 2 mmol/L D,L -homocysteine for 1.5, 5, 10, 20, 30, and 60 minutes, and the active forms of MAP kinase were detected with Western immunoblotting. The degree of phosphorylation of MAP kinase was determined by densitometry. RESULTS: D,L -homocysteine stimulated BASMC proliferation by 20% by day 8. MAP kinase phosphorylation was activated as much as six fold by D,L -homocysteine, with a peak at 30 minutes. PD98059, an inhibitor of MAP kinase phosphorylation, inhibited the homocysteine-induced MAP kinase phosphorylation and attenuated the increase in BASMC proliferation. CONCLUSIONS: These data are consistent with the hypothesis that D,L -homocysteine stimulation of BASMC proliferation involves MAP kinase activation.

Animals↗
PubMed2000

Inhibition of phosphatidylinositol 3-kinase and protein kinase C attenuates extracellular matrix protein-induced vascular smooth muscle cell chemotaxis.

PURPOSE: Intimal hyperplasia (IH), a significant cause of vascular reconstructive failure, is characterized by abnormal vascular smooth muscle cell (VSMC) migration, proliferation, and extracellular matrix (ECM) deposition. The ECM proteins, thrombospondin-1 (TSP-1), fibronectin (Fn), and vitronectin (Vn) can induce VSMC migration; however, the cellular signaling pathways involved are not identical for each ECM protein. Phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) are two enzymes that have been associated with VSMC migration. We sought to elucidate the roles of these enzymes in TSP-1-, Fn-, and Vn-stimulated VSMC migration. METHODS: Chemotaxis assays were performed by using a modified Boyden Chamber. TSP-1, Fn, or Vn (20 microg/mL) or serum-free media (SFM) was placed in the bottom wells of the chamber. Quiescent bovine aortic VSMC were preincubated with LY 294002 (100 micromol/L), a PI3K inhibitor, bisindolylmaleimide I (GF 109203X, 1 micromol/L), a PKC inhibitor, or in SFM alone for 30 minutes. VSMCs (50,000 cells per well) were then placed in the top wells of the chamber, and the assay was conducted for 4 hours at 37 degrees C. Results were recorded as the number of cells migrated per five fields (400x) and analyzed by means of the paired t test, with P value less than.05 considered to be significant (n = 3). RESULTS: The VSMC migration was significantly increased by TSP-1, Fn, and Vn. LY 294002 inhibited TSP-1-, Fn-, and Vn-stimulated VSMC migration (85% to 89%, P <.05). GF 109203X inhibited only TSP-1-stimulated migration (65%, P <.05). CONCLUSION: These results suggest that TSP-1-, Fn-, and Vn-stimulated migration is at least partially dependent on PI3K. However, only TSP-1 stimulated migration is at least partially dependent on PKC.

Animals↗