Smooth Muscle Component Research Articles

PRACTICAL SURGICAL ANATOMY FOR RADICAL PROSTATECTOMY

Practical guidelines in surgical anatomy for radical prostatectomy can be summarized as follows: 1. There is significant individual variation in the anatomy of the male pelvis. 2. The prostate is covered anteriorly by a prominent detrusor apron. 3. Prostates vary with respect to size and shape. 4. BPH compresses and flattens the peripheral zone. 5. In reality, the puboprostatic ligaments are pubovesical ligaments. 6. The dorsal vein complex of the penis is a neurovascular plexus of veins, arteries, and nerves situated primarily ventral to the prostate and urethra. 7. The urethra from the verumontanum to the penile bulb is sphincteric, with its smooth muscle and elastic tissue components primarily responsible for postprostatectomy urinary continence. 8. Multiple micropedicles tether the neurovascular bundles along the entire posterolateral aspect of the prostate.

Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid and nitric oxide systems

Changes in vascular responsiveness are proposed as the basis for some of the cardiovascular complications in cholestasis. Cholestasis is also associated with accumulation of endogenous opioid peptides and evidence of overproduction of nitric oxide (NO). The possible role of NO or opioid system in cholestasis-induced mesenteric vascular bed responsiveness was investigated. Bile duct-ligated and sham-operated rats were treated for 6 days with either normal saline, naltrexone, an opioid antagonist (20 mg/kg/day) or l-NAME ( N(ω)-nitro- l-arginine methyl ester), a nitric oxide synthase inhibitor (3 mg/kg/day). After 7 days, the superior mesenteric artery was cannulated and the mesenteric vascular bed was perfused according to the McGregor method. Baseline perfusion pressure of the mesenteric vascular bed was decreased in bile duct-ligated compared to sham-operated animals. ED 50 of phenylephrine-induced vasoconstriction was increased, but vasoconstriction R max was not different in the vascular bed of bile duct-ligated rats and of sham-operated ones. Acetylcholine-induced vasorelaxation was impaired in bile duct-ligated rats (increased ED 50 and decreased vasorelaxation R max). Sodium nitroprusside-induced vasorelaxation was not different between bile duct-ligated and sham-operated rats, implying that the smooth muscle components of vasorelaxation were intact. Chronic treatment with l-NAME partially restored both the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction response in bile duct-ligated rats. Naltrexone treatment also partially restored the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in bile duct-ligated rats. There is impaired acetylcholine-induced vasorelaxation in cholestatic rats, probably due to a defect in endothelial function. This study also provided evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced vascular hyporesponsiveness.

Steroid-sensitive gene-1 is an androgen-regulated gene expressed in prostatic smooth muscle cells in vivo.

Steroid-sensitive gene-1 (SSG1) is a novel gene we cloned, found regulated by 17beta-estradiol in the rat uterus and mammary gland, and over-expressed in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors. We show here that SSG1 mRNA and protein expression are regulated by androgens in the rat ventral prostate. Increases in SSG1 mRNA levels were detected by Northern blotting after 24 h and reached a 27-fold peak 96 h following castration, relative to SSG1 mRNA expression in sham-operated rats. Dihydrotestosterone or testosterone supplementation of castrated rats prevented this rise in SSG1 mRNA. In contrast with SSG1 mRNA expression, SSG1 protein was decreased 16-fold 2 weeks following castration but was at control levels in the prostates of castrated rats receiving dihydrotestosterone or testosterone. Although SSG1 is regulated by androgens in vivo, treatment of LnCap cells with dihydrotestosterone, cyproterone acetate or flutamide did not result in the regulation of SSG1 protein levels in vitro. Immunofluorescence studies show that SSG1 is mainly expressed in prostatic smooth muscle cells. These results indicate that SSG1 is an androgen-regulated gene that is expressed in the smooth muscle component of the rat ventral prostate in vivo.

Effects of a new steroidal aromatase inhibitor, TZA-2237, and/or chlormadinone acetate on hormone-induced and spontaneous canine benign prostatic hyperplasia.

It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated. (1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X). Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly. TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.

Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in chronically instrumented dogs.

The objective was to investigate the effects of propofol anesthesia on the pulmonary vascular response to endothelium-dependent and -independent vasodilators, compared with the responses measured in the conscious state. Twenty-six conditioned, male, mongrel dogs were instrumented long-term to measure the left pulmonary vascular pressure-flow relation. Pressure-flow plots were measured on separate days in conscious and propofol-anesthetized (5.0 mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after preconstriction with the thromboxane mimetic U46619, and during the cumulative intravenous administration of endothelium-dependent (acetylcholine and bradykinin) and -independent (proline-nitric oxide) vasodilators. Propofol had no effect on the baseline pressure-flow relation compared with the conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the same degree of preconstriction during propofol anesthesia. The pulmonary vasodilator responses to bradykinin and proline-nitric oxide were similar in the conscious and propofol-anesthetized states. In contrast, the pulmonary vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during propofol anesthesia. The intralipid vehicle for propofol had no effect on the acetylcholine dose-response relation. These results suggest that propofol causes a specific defect in the signal transduction pathway for acetylcholine-induced pulmonary vasodilation. This defect involves the endothelial and not the vascular smooth muscle component of the response.

Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: a clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites.

We report 30 uterine tumors composed of an admixture of endometrioid glands, endometrioid stroma, and smooth muscle that lacked the characteristic features of atypical polypoid adenomyoma. The patients ranged from 26 to 64 (median 47) years of age. The usual presenting symptom was abnormal vaginal bleeding, which was "massive" in two patients. Six patients were treated by polypectomy only, with hysterectomy performed in the remainder. Twenty-seven adenomyomas were in the corpus (22 submucosal, two mural, and three subserosal) and three in the cervix. The subserosal and submucosal examples were polypoid. The tumors were 0.3 to 17 cm in greatest dimension, and firm with cystic areas often present on sectioning. Focal hemorrhage was described in five cases. On microscopic examination, the tumors were composed of glands and cysts lined by endometrial-type epithelium separated by endometrial stroma and smooth muscle, with smooth muscle predominating. Minor foci of tubal-type epithelium (14 cases), mucinous endocervical-type epithelium (2 cases), and squamous epithelium (1 case) were present. The smooth muscle component was cellular in three cases and contained occasional bizarre nuclei in three cases. The epithelial cells were uniformly bland. No mitotic activity was observed in the epithelial or mesenchymal elements in 20 cases. In the remainder, up to 5 mitotic figures/10 high-power fields were observed in the epithelium (3 cases), the stroma and smooth muscle (3 cases), or both compartments (4 cases). Follow-up in 14 cases revealed no recurrence or extrauterine spread in any case. A diagnosis of adenocarcinoma or adenosarcoma was entertained by the submitting pathologist in five of 14 consultation cases. Adenomyomas are unusual benign uterine tumors that can be misdiagnosed, in part, because the lesion has not often received attention in the literature. The most realistic considerations in the differential diagnosis are atypical polypoid adenomyoma and adenosarcoma. The former, by definition, has epithelial atypia and the latter a malignant (usually low grade) stromal component with typically absent or inconspicuous smooth muscle. Distinction of adenomyoma from adenosarcoma may have significant therapeutic implications, particularly in young women.

Continence-preserving anatomic radical retropubic prostatectomy

Introduction. Urinary continence, especially in regard to the time required to regain urinary control after radical prostatectomy, remains a significant complication of the procedure. Technical Considerations. The “no touch” or “avoidance” surgical principles that are the basis for continence-preserving radical prostatectomy primarily focus on the preservation of the following components of the external striated urethral sphincteric complex: the entire circumferential musculature of the rhabdosphincter, the fascial investments (the pubourethral ligaments anterolaterally and median fibrous raphe posteriorly), and the innervation of both the rhabdosphincter by way of the intrapelvic branch of the pudendal nerve (somatic) and the mucosal and smooth muscle components by way of the urethral branch of the inferior hypogastric plexus (autonomic). Conclusions. The clinical impact of preserving the external striated urethral sphincter, its innervation, and its fascial attachments by performing a continence-preserving anatomic retropubic prostatectomy is a shorter time to achieve urinary continence.

Expression of Three Isoforms of cGMP-Binding cGMP-Specific Phosphodiesterase (PDE5) in Human Penile Cavernosum

Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. We report here the cloning of three PDE5 isoforms from human penile tissues. Two of the isoforms were identical to PDE5A1 and PDE5A2, respectively, which had been isolated from nonpenile tissues. The third isoform was novel and hence called PDE5A3. The deduced amino acid sequence of PDE5A3 was the same as the C-terminal 823-residue sequence of PDE5A1 and PDE5A2. While PDE5A1 and A2 isoforms were expressed in all tissues examined, the A3 isoform was confined to tissues with a smooth muscle or cardiac muscle component. When expressed in COS-7 cells, PDE5A1, A2, and A3 isoforms had similar cGMP-catalytic activities with Km of 6.2, 5.75, and 6.06 μM, respectively. Their cGMP-catalytic activities were inhibited by zaprinast with IC50 values of 3.2 μM, 1.3 μM, and 1.6 μM, respectively, and by sildenafil with IC50 of 28, 14, and 13 nM, respectively.

Frequent Estrogen and Progesterone Receptor Immunoreactivity in Renal Angiomyolipomas From Women With Pulmonary Lymphangioleiomyomatosis

To determine whether renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis (LAM) express estrogen receptor (ER) and progesterone receptor (PR). Retrospective study of archival tissue. Twelve women with LAM and angiomyolipomas. Fox Chase Cancer Center. ER and PR expression was studied using immunohistochemistry. The hormonal status of the patients at the time of resection of the angiomyolipoma was determined. Ten of the angiomyolipomas had ER immunoreactivity (83%), and all 12 had PR immunoreactivity (100%). The ER and PR positivity was in the smooth muscle component of the angiomyolipomas only. For five women, pulmonary LAM specimens were also available; two were ER positive (40%), and all five were PR positive (100%). All four angiomyolipomas from women receiving progesterone therapy were ER and PR positive. One tumor from a woman receiving tamoxifen was ER negative and strongly PR positive. One woman was pregnant; her tumor was ER and PR positive. ER and PR expression is frequent in renal angiomyolipoma cells from women with LAM. PR was more consistently present than ER in angiomyolipomas and in LAM. Our data suggest that angiomyolipoma growth could be affected by hormonal factors. If the growth of LAM-associated angiomyolipomas slows during hormonal therapy, there are two potential implications for LAM patients: first, angiomyolipoma size could serve as a measurable indication of response to hormonal therapy; and second, surgical removal of angiomyolipomas might be avoided in some cases.

The distribution of vesicular acetylcholine transporter in the human male genitourinary organs and its co-localization with neuropeptide Y and nitric oxide synthase

Because doubt still remains concerning the distribution of nerves that are unequivocally cholinergic in the human genitourinary organs, we have used a specific marker, namely, an antibody to vesicular acetylcholine transporter (VAChT), to immunolabel cholinergic axons and cell bodies in specimens of urinary bladder, seminal vesicle, vas deferens, and prostate gland obtained from neonates and children post mortem. In addition some sections were double-immunolabeled with VAChT and either neuropeptide Y (NPY) or nitric oxide synthase (NOS). The results demonstrated a rich cholinergic innervation to the muscle coat of the bladder body with a much less prominent, but nonetheless significant, cholinergic innervation to the smooth muscle components of the seminal vesicle, vas deferens, and prostate. Small ganglia were scattered throughout the detrusor muscle of the urinary bladder, approximately 75% of the intramural neurons being VAChT immunoreactive, whereas approximately 95% contained NPY and approximately 40% contained NOS. VAChT immunoreactivity was observed in 40% of neurons in ganglia scattered throughout the pelvic plexus. Almost all these cholinergic neurons contained NPY and approximately 65% contained NOS. Almost all the cholinergic nerve fibers throughout the genitourinary organs also contained NPY. Although NOS was sparse in the cholinergic nerves of the bladder body, it occurred in the majority of cholinergic nerves at the bladder neck and was also present in a proportion of the cholinergic nerves in the other organs examined. VAChT-immunoreactive nerves were also observed in a sub-epithelial location in all the organs examined, the majority containing NPY, whereas a small proportion contained NOS. Although doubt remains about the function of sub-epithelial cholinergic nerves in the urinary bladder, the majority of similar nerves in the seminal vesicle, vas deferens, and prostate gland are considered to be secretomotor. Collectively these findings demonstrate that the cholinergic innervation of the male genitourinary system is well established in the neonate and child. Neurourol. Urodynam. 19:185-194, 2000.

THE DISPUTE ABOUT THE EXTERNAL SPHINCTER AND THE UROGENITAL DIAPHRAGM

Basic scientific facts, such as anatomical structures, are rarely subjected to critical reappraisal. Nevertheless, several clinical phenomena exist which are inconsistent with the description of the anatomy of the so-called external sphincter muscle and urogenital diaphragm. We performed a global examination of the anatomy of the entire lower urinary tract in 50 male autopsy specimens. For comparison magnetic resonance imaging of the same regions was performed on 12 healthy patients. Direct comparison of the results of both methods revealed the exact same topography of the bladder neck. The external sphincter or musculus sphincter urethrae is an independent morphological unit separated from the surrounding pelvic floor muscles by connective tissue. The musculus transversus perinei profundus or deep transverse perineal muscle, which is believed to constitute the major element of the urogenital diaphragm, does not exist. There is histomorphological evidence that the external sphincter consists of a striated (musculus sphincter urethrae transversostriatus) and smooth muscle (musculus sphincter urethrae glaber) component.

Molecular analysis of clonality of sporadic angiomyolipoma.

Angiomyolipoma, which consists of three intimately intermixed components, smooth muscle, blood vessels, and adipose tissue, is variably considered a hamartoma, a choristoma or a true neoplasm. This study has investigated the clonality of sporadic angiomyolipomas in seven women, each with a single lesion, by determining the pattern of X-chromosome inactivation. Polymerase chain reaction (PCR) amplification of the highly polymorphic human androgen receptor gene (HUMARA) was performed on the DNA extracted from the paraffin-embedded lesional tissue microdissected to sample the admixed smooth muscle and blood vessel component (SMC/BV) and the adipose tissue component. All seven patients were heterozygous for HUMARA polymorphism upon amplification of undigested DNA from non-lesional tissue and were therefore informative for further analysis. In all patients, lesional DNA, representative of the components, was predigested with HpaII restriction enzyme for amplification of the methylated allele. In six patients, the lesions were clonal, while in one, polyclonal. The polyclonal lesion was small and had less than 20 per cent SMC/BV component. Microdissected SMC/BV component was clonal in 6/7 lesions; the scanty SMC/BV in the remaining lesion did not yield amplifiable DNA. Microdissected adipose tissue was polyclonal in all seven lesions. Angiomyolipomas are three clonal lesions due to a clonal smooth muscle cell and blood vessel component, while the polyclonal adipose tissue is probably metaplastic or reactive.

Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases.

We reviewed 46 cases of renal angiomyolipoma covering the period from 1977 to 1997. Eight cases were associated with tuberous sclerosis and one with lymphangiomyomatosis. Histologically, the lesions were most often classic with the three usual components, i.e., mature adipose tissue, thick-walled blood vessels, and smooth muscle. Seven cases were particularly misleading: three cases were entirely adipose mimicking liposarcoma: two cases had an exclusively smooth-muscle component, one mimicking lymphangiomyomatosis and one with epithelioid cells; another case had a monophasic epithelioid pleomorphic component ("REON": renal epithelioid oxyphilic neoplasm) and proved to be fatal; and another case was associated with collecting duct carcinoma. The immunohistochemical profile showed the coexpression of alpha-smooth-muscle actin and HMB45. Our study is the first to show positivity of estrogen and progesteron receptors or both in more than 25% of cases. Of 35 cases with follow-up information, only one patient died of malignant spread of angiomyolipoma.

α1-Adrenoceptors in Urethral Function

The external urethral sphincteric mechanism generates forces which seal the urethra and can be measured as urethral pressure. Resting pressure can be augmented transiently through a reflex pathway during increases in intra-abdominal pressure. The exact role of the various components of the urethral wall that generate this pressure is so far unknown. Urethral contributions to continence come from the mucosal hermetic seal, the submucosa and its vascular filling and the smooth and striated muscle. In humans α₁-adrenoceptor antagonists can reduce urethral pressure, whereas agonists have little effect. A significant part of urethral resting tone is thought to be mediated through the smooth muscles. In vitro, longitudinal and circular smooth muscle components possess spontaneous tone and are innervated by excitatory and inhibitory nerves. Both types possess α₁-adrenoceptors and contract on stimulation of intrinsic sympathetic nerves or application of α₁-adrenoceptor agonists. In human urethra, longitudinal smooth muscle predominates but its functional role is unclear. α₁ stimulation may also affect the vasculature of the submucosa, the striated muscle of the urethra or transmitter release from neurones in the control pathways. Insufficient knowledge of α₁-adrenoceptor distribution and function within the urethra and the surrounding tissues currently prevents accurate prediction of the therapeutic potential of α₁-adrenoceptor ligands.

Low-Grade Endometrial Stromal Sarcoma with Intracardiac Extension: Evolution of Extensive Smooth Muscle Differentiation and Usefulness of Immunohistochemistry for Its Recognition and Distinction from Intravenous Leiomyomatosis

This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.

Developmental aspects of the contractile smooth muscle component in small intestinal submucosa regenerated urinary bladder.

Urinary bladder reconstruction through bladder regeneration requires the use of a material that is readily available, increases bladder volume and compliance, does not violate the gastrointestinal tract, and is non-immunogenic. The major obstacle has been developing a biomaterial, either permanent or biodegradable, that will function as a suitable scaffold to allow the natural process of regeneration to occur.KeywordsMuscle StripSmall Intestinal SubmucosaDetrusor Smooth MuscleBladder AugmentationContractile Smooth MuscleThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Epithelioid Angiomyolipoma of the Kidney. A Report of Five Cases With a Prominent and Diagnostically Confusing Epithelioid Smooth Muscle Component

Epithelioid Angiomyolipoma of the Kidney. A Report of Five Cases With a Prominent and Diagnostically Confusing Epithelioid Smooth Muscle Component

Epithelioid Angiomyolipoma of the Kidney. A Report of Five Cases With a Prominent and Diagnostically Confusing Epithelioid Smooth Muscle Component

No AccessJournal of UrologyUrological Survey: Abstracts: Renal Tumors, Retroperitoneum, Ureter, and Urinary Diversion and Reconstruction1 Nov 1998Epithelioid Angiomyolipoma of the Kidney. A Report of Five Cases With a Prominent and Diagnostically Confusing Epithelioid Smooth Muscle Component J.N. Eble, M.B. Amin, and R.H. Young J.N. EbleJ.N. Eble More articles by this author , M.B. AminM.B. Amin More articles by this author , and R.H. YoungR.H. Young More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62492-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Epithelioid Angiomyolipoma of the Kidney. A Report of Five Cases With a Prominent and Diagnostically Confusing Epithelioid Smooth Muscle Component." The Journal of Urology, 160(5), pp. 1954–1955 Indiana University School of Medicine and Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, Henry Ford Hospital, Detroit, Michigan, and Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 160Issue 5November 1998Page: 1954-1955 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information J.N. Eble More articles by this author M.B. Amin More articles by this author R.H. Young More articles by this author Expand All Advertisement Loading ...

Endoluminal Sonographic Evaluation of Ureteral and Renal Pelvic Neoplasms

Endoluminal Sonographic Evaluation of Ureteral and Renal Pelvic Neoplasms

Vitamin E and Atherosclerosis

Vitamin E was advocated as an effective treatment for heart disease by Dr. Even Shute of London, Ontario more than 50 years ago. His pioneering claims, which were unacceptable to the medical community at large, have been confirmed by recent findings from epidemiologic studies and clinical trials. This review integrates our current knowledge of atherogenesis with the biological functions of vitamin E. The response-to-injury hypothesis explains atherosclerosis as a chronic inflammatory response to injury of the endothelium, which leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components. Inflammatory and other stimuli trigger an overproduction of free radicals, which promote peroxidation of lipids in LDL trapped in the subendothelial space. Products of LDL oxidation are bioactive, and they induce endothelial expression and secretion of cytokines, growth factors and several cell surface adhesion molecules. The last-mentioned are capable of recruiting circulating monocytes and T lymphocytes into the intima where monocytes are differentiated into macrophages, the precursor of foam cells. In response to the growth factors and cytokines, smooth muscle cells proliferate in the intima, resulting in the narrowing of the lumen. Oxidized LDL can also inhibit endothelial production of prostacyclin and nitric oxide, two potent autacoids that are vasodilators and inhibitors of platelet aggregation. Evidence is presented that vitamin E is protective against the development of atherosclerosis. Vitamin E enrichment has been shown to retard LDL oxidation, inhibit the proliferation of smooth muscle cells, inhibit platelet adhesion and aggregation, inhibit the expression and function of adhesion molecules, attenuate the synthesis of leukotrienes and potentiate the release of prostacyclin through up-regulating the expression of cytosolic phospholipase A2 and cyclooxygenase. Collectively, these biological functions of vitamin E may account for its protection against the development of atherosclerosis.