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PubMed2000

Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism.

UNLABELLED: Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in chronic renal insufficiency (CRI) is characterized by multiglandular hyperplasia. METHODS: In this study, we investigated the effects of the calcimimetic NPS R-568 on the parathyroid gland in rats with CRI induced by ligation of the renal arteries and severe secondary HPT induced by dietary phosphorus loading. Six days after surgery, high-phosphorus diet feeding was started, and NPS R-568 was administered to the rats for 56 days either by daily gavage (30 or 100 micromol/kg) or by continuous subcutaneous infusion (20 micromol/kg. day). RESULTS: After 54 days, serum PTH levels in vehicle-treated CRI rats were 1019 vs. 104 pg/mL in sham-operated controls. Infusion of NPS R-568 maintained serum PTH at levels comparable with those of sham-operated controls, whereas daily gavage also prevented much of the increase in CRI controls and decreased PTH levels intermittently in a dose-dependent fashion. Parathyroid gland enlargement was caused predominantly by hyperplasia. Total cell number per kg body wt was 3.5-fold higher in vehicle-treated CRI rats than in sham-operated controls. Both infusion and high-dose gavage of NPS R-568 completely prevented the increase in parathyroid cell number. CONCLUSION: These results demonstrate that the calcimimetic compound NPS R-568 can prevent both the increase in serum PTH levels and parathyroid hyperplasia in rats with CRI and severe secondary HPT. Moreover, these changes occurred despite decreases in serum 1, 25(OH)2D3 and increases in serum phosphate, suggesting a dominant role for the calcium receptor in regulating parathyroid cell proliferation.

Aniline Compounds↗
PubMed2001

Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor.

BACKGROUND: Recent evidence points to a relationship between the down-regulation of the calcium-sensing receptor (CaR) and parathyroid cell hyperplasia that is associated with chronic renal failure. It is not known, however, if down-regulation of the CaR precedes, and perhaps initiates, parathyroid cell proliferation, or if a decrease in the expression of the CaR occurs subsequently to hyperplasia or the conditions promoting it. The current study examined the temporal relationship of these two events. METHODS: Rats were made uremic by subtotal nephrectomy and were (1) placed immediately on a high phosphate (HP) diet that promotes parathyroid gland hyperplasia, or (2) maintained on a low phosphate (LP) diet that inhibits development of secondary hyperparathyroidism before being switched to the HP diet. Serum chemistries and parathyroid gland (PTG) weights were examined; CaR content and parathyroid cell proliferation (PCNA/Ki-67) were analyzed by immunohistochemistry. RESULTS: When rats were nephrectomized and placed immediately on a HP diet, parathyroid cell proliferation was significantly increased by day 2 and continued to increase at day 4. CaR content was unchanged at 1 and 2 days post-nephrectomy, but fell by day 4. When nephrectomized rats were maintained for 1 week on a LP diet, then switched to a HP diet, an increase in parathyroid cell proliferation was again seen at day 2; down-regulation of the CaR did not occur until after 7 days of uremia and the HP diet. CONCLUSION: These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremic rat model.

Animals↗
PubMed2002

Hyperplasia of the parathyroid gland without secondary hyperparathyroidism.

BACKGROUND: Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG hyperplasia. METHODS: Normal and 5/6 nephrectomized rats were fed a high P (0.8%) diet. After two weeks, the normal rats and half of the uremic rats were sacrificed (U-HP) while the remaining uremic rats were switched to a low P (0.2%) diet (U-HP-LP). RESULTS: High dietary P induced a significant increase in serum P, PTH, and PTG weight, but not ionized calcium compared to normal animals fed the same diet (N-HP). P restriction returned serum P and PTH to normal levels by one week. In contrast, PTG size did not regress and glands remained enlarged for up to eight weeks with no evidence of apoptosis. Ribonuclease protection assay and metabolic labeling studies demonstrated similar PTH/actin mRNA ratios and 35S-labeled PTH among the three groups. Intracellular intact PTH was higher in U-HP and U-HP-LP rats compared to N-HP animals with no differences between the two uremic groups. PTG-PTH content correlated only with PTG weight, and serum PTH only with serum P. The PTG secretory response to calcium remained intact. CONCLUSIONS: In established chief-cell hyperplasia, P restriction restores normal serum PTH levels without affecting PTG hyperplasia, PTH synthesis, PTG cytosolic PTH or the PTH secretory response to calcium, suggesting an impaired exocytosis of PTH.

Animals↗
PubMedDate not supplied

Risk factors for endometrial hyperplasia: results from a case-control study.

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35-73 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990-99 were examined. Controls were 258 non hysterectomized women aged 36-74 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related. Cases with EH were more educated than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7-4.8), more frequently obese (OR 2.7, 95% CI 1.5-5.0) and diabetic (OR 2.4, 95% CI 0.8-6.9). Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an increased risk of EH, but the associations were not statistically significant. Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1-0.5) for postmenopausal ones. Compared to women reporting menopause at age 50 or less, the OR of endometrial hyperplasia was 1.5 (95% CI 0.6-3.5) and 2.2 (95%CI 0.7-6.7), respectively, in women with menopause at age 50-52 and > or = 53. Considering postmenopausal women only the OR was 3.1 (95% CI 1.1-9.3) for use of hormonal replacement therapy (HRT). We conclude that this study indicates that high education, obesity, diabetes, and HRT use increase the risk of endometrial hyperplasia.

Adult↗
PubMed2001

Optimal management of endometrial hyperplasia.

The optimal management of endometrial hyperplasia is the subject of considerable debate. In this chapter the development of our current classification of endometrial hyperplasias is outlined in some detail in order to give an understanding of the complexity of the problem of determining the malignant potential of the hyperplasia which is the central issue in determining optimal treatment. While hysterectomy is still the definitive treatment for older women with hyperplasia, conservative therapy is perfectly acceptable in a defined group of younger women who are closely monitored.

Contraceptives, Oral, Combined↗
PubMed2002

Homocysteine in myointimal hyperplasia.

INTRODUCTION: homocysteine, a sulphur-containing non-essential amino acid, appears to play a role in the pathophysiology of atherosclerosis. However, its role in myointimal hyperplasia, the cause of almost 30% of failures of interventional therapeutic procedures, is much less clear. METHODS: a review of the published scientific data concerning the role of homocysteine in myointimal hyperplasia was performed using MEDLINE and other on-line databases. Evidence was sought from cell culture experiments, animal models and clinical studies. RESULTS: several clinical studies have recently been published linking plasma homocysteine levels to restenosis in coronary and peripheral arterial disease. However, several contradictory studies also exist making the role of homocysteine unclear. There are currently no published randomised trials. Cell culture and animal model experiments have elucidated several potential mechanisms by which may stimulate myointimal hyperplasia. Possible mechanisms include endothelial cell activation with the enhanced release of inflammatory cytokines and growth factors and a direct effect on vascular smooth muscle cell migration and proliferation. CONCLUSIONS: further studies are required before the true role of homocysteine in the pathogenesis of myointimal hyperplasia can be clearly evaluated. If evidence does confirm a role, the ease with which homocysteine levels can be normalised makes it an attractive alternative therapeutic target for intervention.

Animals↗
PubMed1999

Levandoski panographic analysis in the diagnosis of hyperplasia of the coronoid process.

The Levandoski panographic analysis of routine panoramic radiographs was developed to improve the diagnosis of hyperplasia of the coronoid process. The ratio of the length of the coronoid process to the condylar process in the Levandoski panographic analysis has a linear relationship with that in the cephalometric analysis (r = 0.75, n = 59). The ratio in patients with hyperplasia of the bilateral coronoid process was significantly greater than that of the control on both sides (P < 0.01). Although the minimum value of ratio in the patients was 1.15, the maximum value of the controls was 1.07. These results show that the Levandoski panographic analysis is useful in the evaluation of hyperplasia of the coronoid process in adults. When a patient complains of limited mouth-opening and the ratio is more than 1.1, further investigations should be made to verify the diagnosis of hyperplasia of the coronoid process.

Adult↗
PubMed1985

Late-onset adrenal hyperplasia in hirsutism.

We studied the incidence of late-onset adrenal hyperplasia as a cause of hirsutism, its association with the major histocompatibility complex, and its clinical expression. Twenty-four of 400 women seen because of hirsutism were found to have late-onset adrenal hyperplasia, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, and its marked increase after ACTH stimulation. The degree of hirsutism varied widely. Plasma antigen levels were high, especially the level of androstenedione, whereas 5 alpha-reductase activity, considered to be a good index of peripheral androgen utilization, showed frequent normal or low values. The 24 patients were genotyped, along with 84 family members, and plasma hormones were measured in the family members. We found a high correlation between late-onset adrenal hyperplasia and HLA antigens B14 and Aw33. Similar biologic profiles were observed in the patients and those of their siblings who were HLA identical (n = 9), confirming that late-onset adrenal hyperplasia is linked to the histocompatibility complex. These nine siblings had no hirsutism. We therefore conclude that the role of skin sensitivity to androgens is important in determining the clinical expression of this disorder.

17-alpha-Hydroxyprogesterone↗
PubMed1987

The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia.

We examined the influence of androgens on benign prostatic hyperplasia, using nafarelin acetate, a potent luteinizing-hormone-releasing hormone agonist, to achieve reversible androgen deprivation in men with benign prostatic hyperplasia. Nine patients with bladder-outlet obstruction due to benign prostatic hyperplasia were treated with subcutaneous nafarelin acetate (400 micrograms per day) in an open trial for six months. In all patients, serum testosterone decreased to castrate levels. Objective observations included uroflowmetry, measurement of residual urine volume, determination of prostatic size by ultrasonography, and prostatic biopsy. In all patients, the prostate regressed to a mean (+/- SEM) of 75.8 +/- 3 percent of the initial size (range, 52 to 86; P less than 0.005); the regression reached a plateau after four months. Morphologic analysis of biopsy specimens showed regression of glandular epithelium. Three of nine patients had clinical improvement with treatment. Six months after the cessation of treatment, plasma testosterone levels had returned to normal and the size of the prostate had increased to 99 +/- 5.5 percent of the initial size. These findings suggest that androgens have an important supportive role in established benign prostatic hyperplasia and that testicular suppression will benefit some patients. However, this form of treatment could be applicable only in carefully selected patients who were not surgical candidates, and it would need to be maintained indefinitely.

Aged↗
PubMed1992

The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS: In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS: As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

5-alpha Reductase Inhibitors↗
PubMed2000

Elucidating the pulsed-dye laser treatment of sebaceous hyperplasia in vivo with real-time confocal scanning laser microscopy.

BACKGROUND: Several case reports document successful treatment of sebaceous hyperplasia with the pulsed-dye laser. Moreover, noninvasive real-time confocal laser scanning microscopy elucidates the vascular nature of these lesions and their pathophysiologic response to treatment mediated by vessel coagulation. METHODS: Ten patients with 29 lesions of sebaceous hyperplasia were treated with 3 stacked 5-mm pulses of the 585-nm pulsed-dye laser at fluences of 7 or 7.5 J/cm(2). Confocal imaging was performed before and immediately after treatment, as well as at 2, 4, and 8 weeks of follow-up. RESULTS: The great majority of lesions responded to one treatment, with complete disappearance in 28%, decrease in diameter in 66%, and flattening in 93%. Although 28% recrudesced after initial involution, only 7% recurred completely. Three lesions became eroded or crusted, and 7 experienced cutaneous depressions before complete healing, but no scarring or pigmentary side effects were noted. Confocal imaging revealed a prominent "crown" of blood vessels surrounding the sebaceous duct and coagulation of these vessels with pulsed-dye laser treatment. However, the vessels reappeared during follow-up, and no noticeable morphologic changes in the sebaceous duct were noted. CONCLUSION: Vascular targeting of sebaceous hyperplasia can be monitored with real-time reflectance confocal microscopy. Most sebaceous hyperplasia regresses after one treatment with 3 stacked pulses of the 585-nm pulsed-dye laser. Whether this response is due to temporary ischemia induced by selective vessel destruction or nonspecific thermal diffusion beyond the vessels from pulse stacking has not been determined.

Adult↗
PubMed2000

21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study.

OBJECTIVE: Our aim was to determine whether the clinical features of 21-hydroxylase-deficient nonclassic adrenal hyperplasia are correlated with either age at symptom onset or age at presentation, or both, and with the degree of adrenocortical abnormality. STUDY DESIGN: In a multicenter cohort design 220 women with nonclassic adrenal hyperplasia, with a basal or adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level >30.3 nmol/L, were studied, either prospectively (n = 39) or retrospectively (n = 181). Patients were stratified by age of presentation into 5 groups: (1) <10 years (n = 25), (2) 10 to 19 years (n = 64), (3) 20 to 29 years (n = 83), (4) 30 to 39 years (n = 30), and (5) 40 to 49 years (n = 16). Two patients >50 years old were excluded from the analysis because of age. RESULTS: Ninety-two percent of patients <10 years old had premature pubarche at presentation, whereas clitoromegaly and acne were each present in only 20% of these younger subjects. With only patients > or =10 years old considered, presenting clinical features included hirsutism (59%), oligomenorrhea (54%), acne (33%), infertility (13%), clitoromegaly (10%), alopecia (8%), primary amenorrhea (4%), and premature pubarche (4%). Among the patients >/=10 years old, the prevalence but not the degree of hirsutism increased significantly with age. Basal levels of 17-hydroxyprogesterone in adolescents were significantly higher than the levels found either in children (<10 years old) or women 40 to 49 years old (P <.01 and P <.03, respectively), although no difference was noted in the stimulated 17-hydroxyprogesterone levels between age groups. The adrenocorticotropic hormone-stimulated levels but not the basal levels of 17-hydroxyprogesterone were significantly higher in patients with clitoromegaly than in women without clitoromegaly. Alternatively, there were no differences in either basal or stimulated 17-hydroxyprogesterone levels between patients with and those without hirsutism, acne, or alopecia. CONCLUSION: In children <10 years old the most common presenting complaint was premature pubarche, whereas hirsutism and oligomenorrhea were more common in older patients. The prevalence of hirsutism increased with age, suggesting the progressive nature of nonclassic adrenal hyperplasia. Furthermore, the adrenocorticotropic hormone-stimulated levels of 17-hydroxyprogesterone were higher in patients with clitoromegaly, which suggests that the degree of adrenocortical dysfunction in nonclassic adrenal hyperplasia determines, at least in part, the clinical presentation.

17-alpha-Hydroxyprogesterone↗
PubMed2002

Oral contraceptives and the risk of focal nodular hyperplasia of the liver: a case-control study.

OBJECTIVE: A role of female hormones, including oral contraceptives, has been suggested in the etiology of focal nodular hyperplasia of the liver. There is, however, no epidemiologic quantification of this relationship. STUDY DESIGN: A hospital-based case-control study was conducted in Italy of 23 women with histologically confirmed focal nodular hyperplasia of the liver and 94 controls in the hospital for acute diseases. Odds ratios (ORs) were computed by use of multiple logistic regression models. RESULTS: Focal nodular hyperplasia was not associated with menstrual and reproductive factors. Ever oral contraceptive use was reported by 83% of cases and 59% of controls. The multivariate OR was 2.8 (95% confidence interval [CI], 0.8-9.4) for ever use, and 4.5 (95% CI, 1.2-16.9) for use > or = 3 years. The trend in risk with duration was statistically significant. CONCLUSIONS: This study confirms previous clinical observations, and provides a quantitative estimate of the association between use of oral contraceptives and focal nodular hyperplasia of the liver.

Adult↗
PubMed1989

Efficacy of corticosteroids in suppression of intimal hyperplasia.

The effect of steroids and immunosuppression on the development of intimal hyperplasia was studied in 24 New Zealand white rabbits. Staged bilateral arteriotomy and stripping of intima of the common carotid artery was performed by means of a 2F balloon catheter under 700 mm Hg of pressure. At 3 months, after the control side artery was harvested (N = 24), the rabbits were assigned to three groups of eight animals each: (1) dexamethasone 0.1 mg/kg, (2) cyclophosphamide (Cytoxan) 1 mg/kg, or (3) azathioprine 1 mg/kg intramuscularly. The animals were treated on the day before the contralateral intimal stripping and then were treated six times a week for 8 weeks; the vessels were harvested at 3 months. Twelve-week patency rates were 62.5% in the control group, 83.3% in the dexamethasone group, 100% in the Cytoxan group, and only 33.3% in the azathioprine group. The ratio of the luminal area to the area enclosed by the internal elastic lamina was used as an index of intimal hyperplasia, with a higher ratio indicating less intimal thickening. This ratio of the patient vessels was 0.74 +/- 0.14 (N = 15) for the controls, 0.79 +/- 0.11 (N = 6) for the Cytoxan group, and 0.91 +/- 0.06 (N = 5, p less than 0.05) for the dexamethasone group, which is statistically significant by means of analysis of variance. Occluded vessels had evidence of organized thrombus without any intimal hyperplasia. The decrease in intimal hyperplasia seen in the steroid group suggests a potential role for steroids in small vessel revascularization, but further studies are required.

Animals↗
PubMed1993

Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts.

PURPOSE: The purpose of this study was to evaluate the efficacy of three drugs (cilazapril, cyclosporine, and aspirin) in modulating the progression of intimal hyperplasia during short postoperative times in short-segment, autogenous vein bypass grafts in a canine model. The relative effects of the drugs on the progression of intimal hyperplasia were compared with the Gilman parameter, a measure used extensively as a wound healing descriptor. To our knowledge this is the first use of the Gilman parameter in assessing vascular disease. METHODS: Seventy-two conditioned mongrel dogs were randomly and equally divided according to a three-factor analysis of variance. The factors included (1) drug treatments (cilazapril [10 mg/kg/day], cyclosporine [4 mg/kg/day], aspirin [325 mg/day], and control [nonmedicated]), (2) implantation sites (femoral and carotid arteries), and (3) postoperative times of graft harvest (1, 3, and 6 weeks). Each dog had 2 cm segments of autogenous jugular vein interpositioned bilaterally into each of the paired carotid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections. RESULTS: The observed variability in the data was attributed to drug treatments and time. At 1 week after operation the mean Gilman parameters did not differ significantly among the treatment groups in either midgraft or distal graft segments. At 3 weeks the mean Gilman parameters of midgraft and distal graft sections of cyclosporine-treated dogs differed significantly (p < 0.05) from those of the control group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parameters from aspirin- and cyclosporine-treated dogs differed statistically from control and cilazapril-medicated dogs and from each other (p < 0.001). CONCLUSIONS: These data support the efficacy of aspirin and cyclosporine in reducing intimal hyperplasia in short-segment arterialized vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin and cyclosporine persist long-term.

Animals↗
PubMed2001

Endoluminal smooth muscle cell seeding limits intimal hyperplasia.

PURPOSE: Intimal hyperplasia is one of the main responses of the vascular wall to injury. In the current study, we tested the hypothesis that endoluminal seeding of host syngeneic vascular cells could limit intimal hyperplasia induced by either mechanical deendothelialization or chronic allograft rejection in rat aorta. METHODS: An experimental model of in situ seeding of syngeneic endothelial cells, smooth muscle cells (SMCs), and fibroblasts (FIBs) was used in mechanically deendothelialized and allografted aortas. In a preliminary study, the ability of the three cell types (n = 5 per group) to seed on the deendothelialized luminal surface of the aortic wall was evaluated after 2 days, with the use of fluorescent PKH as marker. In the first model, the abdominal aorta of Lewis rats was deendothelialized (n = 6) or deendothelialized and seeded with either SMCs (n = 6) or FIBs (n = 6) before flow was restored. In the allograft model, aortas were harvested from dark agouti rats and orthotopically grafted in Lewis receivers, directly (n = 6) or after deendothelialization. Deendothelialization was performed alone (n = 6) or associated with the seeding of similar host (Lewis) syngeneic SMCs (n = 6) or FIBs (n = 6). Results were evaluated at 2 months with histologic and morphometric methods. RESULTS: SMCs and FIBs were able to adhere in situ to the deendothelialized aortic wall, whereas endothelial cells were not. In mechanically deendothelialized aortas, the seeding of syngeneic SMCs led to a significant reduction in intimal thickness compared with deendothelialized aortas or FIB-seeded aortas (26.9 +/- 1.7 microm vs 55.5 +/- 1.7 and 56.7 +/- 1.7 microm, respectively), and a lower nuclear content (382.2 +/- 35.7 microm(2) vs 779.6 +/- 65.9 and 529.6 +/- 24.3 microm(2), respectively) of neointima. After SMC seeding, intimal hyperplasia was richer in elastin, whereas after FIB seeding it was richer in collagen. In allografts, the seeding of syngeneic SMC led to a significant reduction in intimal thickness compared with control aortas, deendothelialized aortas, or FIB-seeded aortas (31.6 +/- 1.1 microm vs 88.55 +/- 2.8, 74.6 +/- 2.9, and 85.7 +/- 2.6 microm, respectively), and a reduced nuclear content of the neointima (444.9 +/- 23.4 microm(2) vs 1529.1 +/- 116, 972.3 +/- 50, and 645.2 +/- 32.4 microm(2), respectively). Differences observed in the extracellular matrix composition were equivalent to those observed in the mechanically deendothelialized model. CONCLUSIONS: Our results suggest that endoluminal seeding of syngeneic SMCs can be effective in reducing intimal hyperplasia both in a deendothelialization model and in arterial allografts. SMC and FIB endoluminal seeding led to a significatively different accumulation of extracellular matrix in the intima.

Analysis of Variance↗
PubMed2002

Effect of endovascular stent strut geometry on vascular injury, myointimal hyperplasia, and restenosis.

PURPOSE: Early restenosis and the development of myointimal hyperplasia in stented blood vessels have been attributed to deep vascular injury with fracture of the internal elastic lamina (IEL). The purpose of this study was the evaluation of the vascular wall response to superficial injury (without IEL rupture) after balloon angioplasty and intravascular stent placement in porcine arteries and the determination of the effect of stent strut geometry on the degree of vessel injury and early restenosis. METHODS: Balloon-expandable stainless-steel stents were placed into the iliac arteries of 10 Sinclair miniature swine that had been fed an atherogenic diet. A Palmaz stent, with rectangular struts and smooth corners, was randomly assigned to one iliac artery (group 1), and a novel stent, which was designed and manufactured in the laboratory with thicker struts and sharper corners specifically to induce large wall stress concentrations, was placed in the contralateral iliac artery (group 2). Intravascular ultrasound scan was used in all deployments to ensure accurate balloon sizing and to avoid stent overexpansion and deep vascular injury. At 90 days after implantation, the animals were killed, the stented vessels harvested, and histomorphometric analysis performed. RESULTS: Deployment of novel stents in group 2 resulted in a statistically higher incidence rate of deep vascular injury (fracture of the IEL) compared with group 1, despite identical balloon size used for deployment (with Student t test, P <.05). Vessels with deep injury showed a 10-fold increase in myointimal thickening compared with those vessels in which the IEL remained intact. A statistically higher restenosis rate was observed for group 2 (33.5% +/- 19.90%) compared with group 1 (20.39% +/- 14.70%). For both stent designs, there was a trend toward lower degrees of restenosis within the mid-portion of the stent. For superficially injured arteries in both groups, no correlation was observed between the amount of vessel wall/medial layer compression and the development of restenosis from myointimal hyperplasia. CONCLUSION: Maintenance of an intact IEL is an important factor in the prevention of myointimal hyperplasia and restenosis in stented porcine iliac arteries. The alteration of stent strut height and geometry does not significantly affect restenosis and the development of myointimal hyperplasia in vessels with superficial injury. Superficial injury elicits a response that is independent of stent strut geometry and vessel wall compression. Stent strut profile may, however, increase local vessel wall stress concentrations, leading to IEL rupture and an exaggerated response to injury.

Animals↗
PubMed2003

Blockade of the epidermal growth factor receptor decreases intimal hyperplasia in balloon-injured rat carotid artery.

HYPOTHESIS: Arterial intimal hyperplasia is induced by injury and is frequently the cause of luminal narrowing after vascular reconstruction. Smooth muscle cells (SMC) respond to injury by proliferating and migrating into the intima. This process is regulated by thrombin, endothelin, and angiotensin II, all ligands of G protein-coupled receptors. Signal transduction from these receptors in cultured cells depends in part on transactivation of epidermal growth factor receptor (EGFR). We hypothesize that EGFR has a substantial role in activation of SMC in vivo and development of intimal hyperplasia. METHODS: Intimal hyperplasia was induced in rat carotid arteries by passage of a balloon catheter. Animals were given a monoclonal blocking antibody to rat EGFR, matched mouse immunoglobulin G (IgG) control antibody, or saline solution. RESULTS: Blocking EGFR antibody inhibited medial SMC proliferation, as determined by 5-bromo-2'-deoxyuridine labeling at 2 days (IgG control, 8.0% +/- 2.0%; anti-EGFR, 3.2% +/- 0.8%) and intimal hyperplasia at 14 days (intimal area: IgG control, 0.07 +/- 0.01 mm(2); anti-EGFR, 0.04 +/- 0.01 mm(2)). CONCLUSION: Activation of EGFR is important for early induction of SMC proliferation and subsequent intimal thickening.

Animals↗