Six weeks of localized passive heat therapy elicits some exercise-like improvements in resistance artery function.

The purpose of this study was to examine the effects of 6 weeks of localized, muscle-focused (quadriceps femoris) passive heat therapy (PHT) on resistance artery function, exercise haemodynamics and exercise performance relative to knee extension (KE) exercise training (EX). We randomized 34 healthy adults (ages 18-36; n = 17 female, 17 male) to receive either PHT or sham heating sessions (120 min, 3 days/week), or EX (40 min, 3 days/week) over 6 weeks. Blood flow was assessed with Doppler ultrasound of the femoral artery during both passive leg movement (PLM) and a KE graded exercise test. Muscle biopsies were taken from the vastus lateralis at baseline and after 6 weeks. Peak blood flow during PLM increased to the same extent in both the EX (∼10.5% increase, P = 0.009) and PHT groups (∼8.5% increase, P = 0.044). Peak flow during knee extension exercise increased in EX (∼19%, P = 0.005), but did not change in PHT (P = 0.523) and decreased in SHAM (∼7%, P = 0.020). Peak vascular conductance during KE increased by ∼25% in EX (P = 0.030) and PHT (P = 0.012). KE peak power increased in EX by ∼27% (P = 0.001) but did not significantly change in PHT and SHAM groups. Expression of endothelial nitric oxide synthase increased significantly in both EX (P = 0.028) and PHT (P = 0.0095), but only EX resulted in increased angiogenesis. In conclusion, 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not yield significant improvements in performance. KEY POINTS: Many for whom exercise would be most beneficial are either unable to exercise or have a very low exercise tolerance. In these cases, an alternative treatment to combat declines in resistance artery function is needed. We tested the hypothesis that passive heat therapy (PHT) would increase resistance artery function, improve exercise haemodynamics and enhance exercise performance compared to a sham treatment, but less than aerobic exercise training. This report shows that 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not improve exercise performance. Additionally, muscle biopsy analyses revealed that endothelial nitric oxide synthase expression increased in both PHT and exercise training groups, but only exercise resulted in increased angiogenesis. Our data demonstrate the efficacy of applying passive heat as an alternative treatment to improve resistance artery function for those unable to receive the benefits of regular exercise.

Sex Differences in Track and Field Elite Youth.

PURPOSE: To understand athletic performance before and after puberty, this study determined 1) the age at which the sex difference increases among elite youth track and field athletes for running and jumping events, and 2) whether there is a sex difference in performance before ages associated with puberty among elite youth athletes. METHODS: Track and field records of elite US male and female youth (7-18 yr) across 3 yr (2019, 2021, and 2022) were collected from an online database ( athletic.net ). The top 50 performances were recorded for 100-, 200-, 400-, and 800-m track running, long jump, and high jump. RESULTS: Males ran faster than females at every age in the 100, 200, 400 and 800 m ( P < 0.001). When combining all running events, the sex difference (%) was 4.0% ± 1.7% between 7 and 12 yr and increased to 6.3% ± 1.1% at 13 yr and 12.6% ± 1.8% at 18 yr ( P < 0.001). Similarly, males jumped higher and farther than females at every age ( P < 0.001). For long jump, the sex difference was 6.8% ± 2.8% between 7 and 12 yr, increasing to 8.5% ± 1.7% at 13 yr and 22.7% ± 1.4% at 18 yr ( P < 0.001). For high jump, the sex difference was 5.3% ± 5.2% between 7 and 12 yr, increasing to 12.4% ± 2.9% at 15 yr and 18.4% ± 2.04% at 18 yr ( P < 0.001). CONCLUSIONS: Before 12 yr of age in elite youth track and field athletes, there was a consistent and significant sex difference of ~5%, such that males ran faster and jumped higher and farther than females. The magnitude of the sex difference in performance increased markedly at 12-13 yr for running and long jump and 14 yr for high jump and thus was more pronounced after ages associated with puberty.

Underrepresentation of women in exercise science and physiology research is associated with authorship gender.

Historically, low representation of women participants in exercise science and physiology studies has led to a lack of understanding in the response of women to exercise and therapeutic interventions. We hypothesized that 1) the number of women authors, participants, and editorial board members increased over 30 years (1991-2021) and 2) larger representation of women as editors and authors is associated with more women participants. Gender (man/woman) of editorial board members (n = 394), authors (n = 5,735), and participants (n = 2,984,883) of 972 original research articles with human participants published in 1991 and 2021 was analyzed from three journals: Journal of Applied Physiology, Medicine and Science in Sports and Exercise, and British Journal of Sports Medicine. Between 1991 to 2021, the average percent women per article as participants (21.9 ± 31.7% vs. 36.3 ± 30.3%, respectively, P < 0.001), authors (16.4 ± 22.4% vs. 30.9 ± 24.0%, P < 0.001), and editorial board members (13.3 ± 5.4% vs. 41.5 ± 7.3%, P = 0.006) increased. In 2021, the gender proportion of participants in large datasets was similar (50.2 ± 20.2% women). However, studies with smaller datasets (i.e., <∼3,000 participants) included less women (35.6 ± 30.6%). Women participants (%) were less when the last author was a man rather than a woman in 1991 (19.9 ± 29.5% vs. 34.3 ± 42.2%) and 2021 (31.6 ± 27.7% vs. 51.7 ± 33.4%). In 2021, there was a positive correlation between author and participant gender (% women) (r = 0.42, P < 0.001). Our data suggest that the low representation of women in exercise science and physiology research could be resolved with equitable numbers of women authors and editors and by encouraging men authors to study both women and men participants.NEW & NOTEWORTHY Analysis of human applied physiology studies revealed that the representation of women authors, participants, and editorial board members increased over 30 years but remained lower than men in 2021. Larger representation of women editors and authors was associated with more women participants. Women authors assessed similar numbers of women and men participants, whereas men authors included less women. Equitable representation of women participants may be achieved by closing the gender gap in authorship and editorial board membership.

The exercise power-duration relationship is equally reproducible in eumenorrheic female and male humans.

This study aims to investigate the effect of the menstrual cycle (MC) on exercise performance across the power-duration relationship (PDR). We hypothesized females would exhibit greater variability in the PDR across the MC than males across a similar timespan, with critical power (CP) and work-prime (W') being lower during the early follicular phase than the late follicular and midluteal phases. Seven eumenorrheic, endurance-trained female adults performed multiple constant-load-to-task-failure and maximum-power tests at three timepoints across the MC (early follicular, late follicular, and midluteal phases). Ten endurance-trained male adults performed the same tests approximately 10 days apart. No differences across the PDR were observed between MC phases (CP: 186.74 ± 31.00 W, P = 0.955, CV = 0.81 ± 0.65%) (W': 7,961.81 ± 2,537.68 J, P = 0.476, CV = 10.48 ± 3.06%). CP was similar for male and female subjects (11.82 ± 1.42 W·kg-1 vs. 11.56 ± 1.51 W·kg-1, respectively) when controlling for leg lean mass. However, W' was larger (P = 0.047) for male subjects (617.28 ± 130.10 J·kg-1) than female subjects (490.03 ± 136.70 J·kg-1) when controlling for leg lean mass. MC phase does not need to be controlled when conducting aerobic endurance performance research on eumenorrheic female subjects without menstrual dysfunction. Nevertheless, several sex differences in the power-duration relationship exist, even after normalizing for body composition. Therefore, previous studies describing the physiology of exercise performance in male subjects may not perfectly describe that of female subjects.NEW & NOTEWORTHY Females are often excluded from exercise performance research due to experimental challenges in controlling for the menstrual cycle (MC), causing uncertainty regarding how the MC impacts female performance. The present study examined the influences that biological sex and the MC have on the power-duration relationship (PDR) by comparing critical power (CP), Work-prime (W'), and maximum power output (PMAX) in males and females. Our data provide evidence that the MC does not influence the PDR and that females exhibit similar reproducibility as males. Thus, when conducting aerobic endurance exercise research on eumenorrheic females without menstrual dysfunction, the phase of the MC does not need to be controlled. Although differences in body composition account for some differences between the sexes, sex differences in W' and PMAX persisted even after normalizing for different metrics of body composition. These data highlight the necessity and feasibility of examining sex differences in performance, as previously generated male-only data within the literature may not apply to female subjects.

Feasibility and acceptability of a telehealth model for autism diagnostic evaluations in children, adolescents, and adults.

This study examined the feasibility and acceptability of a telehealth diagnostic model deployed at an autism center in the southwestern United States to safely provide autism spectrum disorder (ASD) diagnostic evaluations to children, adolescents, and adults during the COVID-19 pandemic. Participants included all clients for whom a telehealth diagnostic evaluation was scheduled at the diagnostic clinic (n = 121) over a 6-month period. Of 121 scheduled clients, 102 (84%) completed the telehealth evaluation. A diagnostic determination was made for 91% of clients (93 out of 102) using only telehealth procedures. Nine participants (two females; ages 3 to 11 years) required an in-person evaluation. Responses from psychologist and parent acceptability surveys indicated the model was acceptable for most clients. Psychologist ratings suggested that telehealth modalities used in the current study may be less acceptable for evaluating school-aged children with subtle presentations compared to children in the early developmental period, adolescents, and adults. Parents of females reported higher acceptability than parents of males. Findings contribute to the small but growing literature on feasibility and acceptability of telehealth evaluations for ASD and have implications for improving access to care during and after the COVID-19 pandemic. LAY SUMMARY: This study described telehealth methods for evaluating children, adolescents, and adults for autism spectrum disorder. Telehealth methods were generally acceptable to psychologists conducting the evaluations and parents of diagnostic clients. Psychologists reported the methods to be less acceptable for school-aged children and parents of males found the methods less acceptable than parents of females. The telehealth methods described may help to increase access to diagnostic professionals and reduce wait times for evaluations during and after the COVID-19 pandemic.

Beliefs about intellectual disability among employees at a state facility and undergraduate students: An exploratory analysis.

BACKGROUND: Individuals with intellectual disability are subject to stigmatization, even among those providing services to them. METHOD: Employees from an intermediate care facility (n = 97) and undergraduate students (n = 92) completed measures on their attitudes, beliefs of etiological causes and endorsement of helpful treatments and supports. RESULTS: Overall, participants reported few stigmatizing attitudes and high levels of support for interventions. Differences between employees and students emerged in regard to attitudes and causal beliefs, with employees reporting more support for sheltering and less endorsement of biomedical causes. Among students, those that reported knowing someone with intellectual disability reported less agreement with causal factors as well as differences in what supports were thought to be necessary or beneficial. CONCLUSIONS: Attitudes and beliefs are interrelated and while familiarity impacts these views, it does not necessarily lead to greater understanding or endorsement of treatments or supports. The effects of familiarity on attitudes and beliefs should continue to be explored.

Effectiveness of Auditory Measures for Detecting Hidden Hearing Loss and/or Cochlear Synaptopathy: A Systematic Review.

Standard audiometric evaluations are not sensitive enough to identify hidden hearing loss (HHL) and/or cochlear synaptopathy (CS). Patients with either of these conditions frequently present with difficulty understanding speech in noise or other complaints such as tinnitus. The purpose of this systematic review is to identify articles in peer-reviewed journals that assessed the sensitivity of audiologic measures for detecting HHL and/or CS, and which showed potential for use in a clinical test battery for these disorders. A reference librarian submitted specific boolean terminology to MEDLINE, Embase, and Web of Science. The authors used a consensus approach with specially designed score sheets for the selection of titles, abstracts, and then articles for inclusion in the systematic review and for quality assessment. Fifteen articles were included in the systematic review. Seven articles involved humans; seven involved animals, and one study used both humans and animals. Results showed that pure-tone audiometry to 20 kHz, otoacoustic emissions, electrocochleography, auditory brainstem response (ABR), electrophysiological tests, speech recognition in noise with and without temporal distortion, interviews, and self-report measures have been used to assess HHL and/or CS. For HHL, ultra-high-frequency audiometry may help identify persons with sensory hair cell loss that does not show up on standard audiograms. Promising nonbehavioral measures for CS included ABR wave I amplitude, the summating potential-to-action potential ratio, and speech recognition in noise with and without temporal distortion. Self-report questionnaires also may help identify auditory dysfunction in persons with normal hearing.

Clinical Instructors' Perspectives on the Clinical Education of Internationally Educated Physical Therapists: Diversity's Impact on the Experience.

Purpose: The aim of this study was to understand the nature and extent of clinical instructors' (CIs') involvement in the clinical education of internationally educated physical therapists (IEPTs) while exploring CIs' perceptions of the similarities among and differences between IEPTs and Canadian-trained students. Method: In this qualitative descriptive study, 13 semi-structured interviews were conducted with CIs who were involved in a bridging programme for IEPTs. Data were coded using NVivo version 10, and common themes emerged through qualitative thematic analysis. Results: The majority of CIs perceived IEPTs' backgrounds to be diverse as a result of their varied previous clinical experience, physiotherapy scope of practice, and life stressors. Their diverse backgrounds contributed to the similarities and differences found in their skills, their personal motivation, and the education process, leading to successes and challenges in the clinical environment. Conclusions: Differences between IEPTs and Canadian-trained students stem from IEPTs' diverse backgrounds. Recognizing this diversity while demonstrating cultural competence will promote a successful clinical experience for both IEPT learners and CIs, which will ultimately facilitate the integration of IEPTs into the Canadian health care system.

Objectif : comprendre la nature et la portée de la participation des enseignants cliniques (EC) à la qualification clinique des physiothérapeutes formés à l'étranger (PTFÉ) tout en examinant leurs perceptions des similarités et des différences entre leur formation et celle des étudiants canadiens. Méthodologie : dans la présente étude descriptive et qualitative, les chercheurs ont effectué 13 entrevues semi-structurées auprès d'EC qui participaient à un programme de qualification destiné aux PTFÉ. Ils ont codé les données au moyen de la version 10 de NVivo et regroupé les thèmes communs à l'aide d'une analyse thématique qualitative. Résultats : la majorité des EC trouvaient le parcours des PTFÉ diversifié en raison de l'hétérogénéité de leurs expériences cliniques antérieures, de la portée de leur pratique et des éléments stressants de la vie. La diversité de ces parcours contribuait à des similarités et à des différences sur le plan des compétences, de la motivation personnelle et du processus de qualification, qui s'associaient à des réussites et des difficultés en milieu clinique. Conclusions : les différences entre les PTFÉ et les étudiants formés au Canada proviennent de l'hétérogénéité des parcours des PTFÉ. La prise de conscience de cette diversité, conjuguée à la compétence culturelle, favorisera une expérience clinique positive, tant pour les PTFÉ que pour les EC. Au bout du compte, elle facilitera l'intégration des PFTÉ au système de santé canadien.

Minocycline plus N-acteylcysteine induces remyelination, synergistically protects oligodendrocytes and modifies neuroinflammation in a rat model of mild traumatic brain injury.

Mild traumatic brain injury afflicts over 2 million people annually and little can be done for the underlying injury. The Food and Drug Administration-approved drugs Minocycline plus N-acetylcysteine (MINO plus NAC) synergistically improved cognition and memory in a rat mild controlled cortical impact (mCCI) model of traumatic brain injury.3 The underlying cellular and molecular mechanisms of the drug combination are unknown. This study addressed the effect of the drug combination on white matter damage and neuroinflammation after mCCI. Brain tissue from mCCI rats given either sham-injury, saline, MINO alone, NAC alone, or MINO plus NAC was investigated via histology and qPCR at four time points (2, 4, 7, and 14 days post-injury) for markers of white matter damage and neuroinflammation. MINO plus NAC synergistically protected resident oligodendrocytes and decreased the number of oligodendrocyte precursor cells. Activation of microglia/macrophages (MP/MG) was synergistically increased in white matter two days post-injury after MINO plus NAC treatment. Patterns of M1 and M2 MP/MG were also altered after treatment. The modulation of neuroinflammation is a potential mechanism to promote remyelination and improve cognition and memory. These data also provide new and important insights into how drug treatments can induce repair after traumatic brain injury.

Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina.

Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas, we used a pharmacological approach that showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12) but not lysine 27 of histone 3 (H3K27) and led to maintained expression of progenitor-specific genes such as Vsx2 and Hes1 with concomitant block of expression of rod-specific genes. ChiP experiments confirmed these changes in the promoters of a group of progenitor genes. Based on our results, we suggest that HDAC1-specific inhibition prevents progenitor cells of the retina from exiting the cell cycle and differentiating. HDAC1 may be an essential epigenetic regulator of the transition from progenitor cells to terminally differentiated photoreceptors.

Nausea, Vomiting, and Weight Loss in a Young Adult Patient With a History of a Gunshot Wound.

Assessing victims of gunshot wounds with retained bullets/bullet fragments for lead toxicity is not always considered until the patient develops signs and symptoms of toxicity. We discuss the case of a 19-year-old young man who received a diagnosis of chronic lead toxicity (serum lead concentration 51 µg/dL) 5 weeks after a hunting accident. Extensive wound debridement occurred following the accident; however, lead toxicity was not diagnosed until after his fourth emergency department visit. Oral chelation therapy was required for the management of his lead toxicity.

A psychotherapeutic baby clinic in a hostel for homeless families: practice and evaluation.

OBJECTIVES: A pilot baby clinic in a hostel for homeless families has been established to address the specific attachment and developmental needs of infants living in temporary accommodation. The aim of this study was to assess whether this clinic model was associated with more positive outcomes than mainstream community services in terms of infant development and parent-infant interactions. DESIGN: Parent-infant psychotherapy and health visiting services collaborated to develop a new model of baby clinic, which reconfigured the traditional clinic to give priority to infants' affective experiences in a therapeutic group setting. Outcomes for parent-infant dyads in a homeless hostel where this service model was applied were compared with outcomes for parents and infants in hostels, which did not have such a service. METHODS: Fifty-nine mother-baby dyads participated in evaluation, 30 in the intervention hostel group and 29 living in comparison hostels. Infant mental and motor development was assessed using the Bayley Scales of Infant Development. Interactions between the parents and infants were video-recorded and coded on the Coding Interactive Behaviour Scales. RESULTS: The indices of mental and motor development of infants in the intervention hostel were significantly improved over time in relation to infants in the comparison hostels. No significant differences were found in the quality of parent-infant interaction between the two groups over time. CONCLUSIONS: The findings indicate that the service model may have positive benefits for infant development. The findings, study limitations, and clinical implications are discussed. PRACTITIONER POINTS: Parents and infants living in temporary accommodation represent a high-risk and hard-to-reach population. A new model of intervention, which combines universal infant health services with a therapeutic parent-infant group may be an effective means of supporting the emotional needs of hard-to-reach parents and infants.

"High five to healthy living": a health intervention program for youth at an inner city community center.

Providing developmental programs to inner-city youth is a key component to promoting healthy lifestyles in urban communities. In this study, 46 adolescents, predominately African American youth (age 11-14), participated in the "High Five for Healthy Living" hygiene intervention program hosted at the NFL Youth Education Town of the Boys and Girls Club of Atlanta. Windshield surveys, key informant interviews and focus groups were conducted in order to identify the needs of the surrounding community and subsequently plan and implement a 5 week developmental module to meet these needs. Weekly modules were conducted focusing on oral hygiene, hand washing, physical activity, male/female personal hygiene, and nutrition/food safety. Surveys administered showed that a large percentage of students exhibited behavioral change following the completion of each module: 42% for oral hygiene, 88% for hand washing, 75% for physical activity, 88% for personal hygiene and 50% for nutrition/food safety. From these findings, it is evident that that African American adolescents can benefit from developmental programs targeted to address their specific community needs, and as a result implement personal lifestyle changes. Such interventions could potentially decrease in the prevalence of certain preventable diseases endemic to many low socioeconomic inner city communities.

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.

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.

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.

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.