Depression mediates the relationship between adverse childhood experiences and risky drinking among Hispanic young adults.

BACKGROUND AND OBJECTIVES: Hispanic young adults in the United States have consistently high rates of risky drinking, adverse childhood experiences (ACEs), depression, and anxiety. There is a positive association between ACEs and alcohol use among Hispanic populations; it is unknown if mental health symptomatology mediates this relationship. The purpose of this study was to test whether depression and anxiety mediated the relationship between ACEs and risky drinking among Hispanic young adults who engage in risky drinking. METHODS: Data from 264 Hispanic young adults, ages 19 to 30, were collected via an online questionnaire. Participants were recruited via social media, emails/listservs across colleges, the community, and web-panels. The questionnaire assessed ACEs, risky drinking, depression, and anxiety. We conducted a mediational analysis to test whether depression and anxiety mediated the relationship between ACEs and risky drinking. RESULTS: Of the sample, 59.8% identified as female and 40.2% as male. The average age was 24.37 (SD = 3.069). Participants (61%) identified as Mexican, Mexican American, or Chicano, and 84.1% identified as second-generation. ACEs were positively associated with risky drinking, depression, and anxiety. Depression mediated the relationship between ACEs and risky drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Depression explained the association between ACEs and risky drinking among Hispanic young adults, adding to our understanding of how mediators can illustrate pathways that lead from ACEs to risky drinking. Practitioners and interventionists should continue supporting Hispanic youth by integrating them into early prevention programs to mitigate the mental health consequences of ACEs that could lead to risky drinking.

Challenges in implementing cultural adaptations of digital health interventions.

Differences in the access and use of digital health interventions are driven by culture, in addition to economic and physical factors. To avoid the systematic exclusion of traditionally underserved cultural groups, creating inclusive digital health interventions is essential. One way to achieve this is through cultural adaptations, defined as the systematic modification of an existing intervention that aligns with a target audience's cultural norms, beliefs, and values. In theory, cultural adaptations can potentially increase the reach and engagement of digital health interventions. However, the evidence of whether and how that is achieved is limited. Justifying, planning, and implementing an adaptation comes with various challenges and takes time and money. This perspective provides a critical overview of the field's current state and emphasizes the need for technology-specific frameworks that address when and how to culturally adapt digital health interventions.

Perceived belonging on campus predicts depression among heavy drinkers: A test of three moderators.

Objective: An association exists between perceived belonging and depression among college students. Because a student's sense of belongingness may vary as a function of their social identity, three identities - ethnicity, first-generation college student status, and sex - were investigated as potential moderators of this relationship. Participants: One hundred eighty-seven heavy-drinking college students (63% female; 52% non-Latinx White; M = 20 years of age) were assessed. Methods: Three hierarchical linear regressions were conducted to test whether belonging at baseline predicted depression at six months and whether each identity variable moderated this association. Results: Analyses yielded significant main effects between belonging and depression. Hispanic nor first-generation status interacted with belonging in predicting depression. Sex interacted with belonging where higher belongingness was associated with lower levels of depression only among female students. Conclusion: Mental health providers should consider asking female students about their perceptions of belonging on college campuses to understand their vulnerability to depression.

Low levels of fitting in on campus moderates the relationship between enhancement drinking motives and drinks per week among college students.

The first year of college is often marked by increased levels of alcohol consumption; first-year students also vary in their sense of fitting in on campus. Research has amply documented the links between social and enhancement drinking motives with various alcohol outcomes among college students. However, it is unclear how perceived levels of fitting in on campus potentially buffers or amplifies the relationship between drinking motives and drinking behavior. We explored whether perceptions of fitting in on campus moderated effects of social and/or enhancement drinking motives on drinks per week. A sample of 121 heavy drinking first year college students (50 % female, 58 % non-Latinx White, M = 18 years of age) were assessed twice in their first semester (baseline, 3 months) in the context of an alcohol-specific intervention. Hierarchical linear regressions were conducted to test whether drinking motives (social and enhancement) at baseline prospectively predicted drinks per week at 3 months. We hypothesized a positive association between both drinking motives and drinks per week; whether fitting in moderates these relationships was exploratory. Regression analyses yielded non-significant main effects of social motives, enhancement motives, and feelings of fitting in on drinks per week. There was no significant interaction for social motives, but the interaction between enhancement motives and fitting in was significant. Participants with a low sense of fitting in had a strong positive relationship between enhancement motives and drinks per week. Improving perceptions of fitting in for first-year college students may potentially reduce the association between enhancement drinking motives and drinks per week.

Latinx Sexual Minority Adolescent Substance Use: State of the Science and Call for Intersectional Minority Stressors and Protective Factors.

Purpose of review: Latinx sexual minority adolescents (LSMA) are at an intersection of ethnic and sexual minority (SM) status and may experience heighten risk of substance use and related problems. These youth may also hold unique protective factors that help mitigate the effects of minority stress and curb substance use. Little is known, however, about the intersectional minority stressors (i.e., due to ethnicity and SM status) and protective factors related to substance use among this population. Recent Findings: According to the minority stress model, there are unique minority stressors and resiliency factors that can help explain differences in behavioral health rates between white SM and SM of color. Research supports the notion that minority stressors (e.g., stigma/risk, homophobic bullying, and family rejection of SM status) confer risk for substance use among LSMA. In terms of resilience, less is known, but there may be some protective factors that have not been measured that could explain lower rates in some substances (i.e., club drugs and methamphetamine). Summary: Little is known about how the intersections of ethnicity and SM status are associated with substance use in adolescence. Future research should assess the temporal relationship of multilevel (i.e., intrapersonal, relational, and system), intersectional (i.e., ethnicity and SM status) minority stressors and protective factors unique to LSMA on substance use. We propose that the findings from these future studies will help to create socioculturally appropriate behavioral health treatments that consider the intersectional risks and strengths within the LSMA population.

Boosting bactericidal immunity of a recombinant Mycobacterium smegmatis strain via zinc-dependent ribosomal proteins.

Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that various strains of the IKEPLUS vaccine confer a higher survival benefit than BCG in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 when IKEPLUS was grown in low zinc and iron containing Sauton medium. We confirmed on biofilm assays that zinc plays a vital role in the growth and formation of Mycobacterium smegmatis ( M. smegmatis ) biofilms. IKEPLUS grown in low zinc media led to better protection of mice after intravenous challenge with very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild type M. smegmatis . We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2 but this did not lead to an increment in the protection mediated by BCG.

Implementing Educational and Systems-Level Changes to Improve Cancer Screening Rates Among State Employees in Missouri.

As of 2022, only 51% of active eligible state employees in Missouri have been screened for colorectal cancer and 67% for breast cancer, despite having state-sponsored health insurance. In fall 2020, the Missouri Department of Health and Senior Services Comprehensive Cancer Program partnered with the Missouri Cancer Consortium to create a strategy to improve cancer screening rates among state employees. The project was designed to include 3 phases: 1) a colorectal cancer education phase, 2) an expanded education phase that included additional cancers, and 3) a proposed intervention phase that will include screening events. In the first phase, in 2020, colorectal cancer educational materials were sent to all state employees. In the second phase, in 2022, educational resources were expanded to include additional cancers and screening tools. In both initiatives, educational materials and information on current screening recommendations were distributed to approximately 40,000 state employees. A database of screening rates was developed to monitor screening rates and challenge state employees to complete screenings. Evidence-informed interventions were implemented with a focus on health equity. We used a regional approach to identify geographic areas with the greatest need. These efforts will support the next phase of the project, which involves planning breast and colorectal cancer screening events. Policy changes will be encouraged to remove systems-level barriers that discourage employees from being screened for cancer. Recommended tools and strategies can be adopted by similar organizations with complex, multitier employee structures.

Results of a Randomized Trial of Screening, Brief Intervention, and Referral to Treatment (SBIRT) to Reduce Alcohol Misuse Among Active-Duty Military Personnel.

OBJECTIVE: Rates of heavy alcohol use among active-duty military personnel in the United States are high and negatively affect individuals within the service branches. This study tested the effectiveness of a military-focused screening, brief intervention, and referral to treatment (SBIRT) intervention for reducing risky alcohol use among active-duty patients. METHOD: We used a randomized, parallel, two-group design to test the effectiveness of the SBIRT intervention in a convenience sample of service members recruited from the emergency department of a military hospital. A total of 791 participants were randomized to the SBIRT or usual care conditions, and 472 participants (59.7%) completed a 6-month follow-up. Fifteen percent of the sample was female. Self-reported Alcohol Use Disorders Identification Test (AUDIT), controlled drinking self-efficacy (CDSE), and readiness to change drinking behaviors were assessed at baseline and follow-up. RESULTS: Among higher risk participants (i.e., AUDIT ≥8), results of a complete case analysis showed a significant reduction in scores on the AUDIT-C (consumption questions from the AUDIT) and a significant increase in CDSE. Null findings were observed for intent-to-treat analyses testing the effectiveness of the SBIRT intervention; significant decreases in AUDIT and AUDIT-C scores and significant increases in CDSE were observed over time, irrespective of condition assignment for both complete case and intent-to-treat analyses. CONCLUSIONS: Results of a complete case analysis provided some support for the effectiveness of the SBIRT intervention for higher risk participants. The results of the more conservative intent-to-treat analyses did not support any of the study hypotheses. Future SBIRT effectiveness trials should also test electronic SBIRT intervention approaches.

A Pilot Study Examining the Efficacy of Delivering Colorectal Cancer Screening Messages via Virtual Health Assistants.

INTRODUCTION: Patients are more likely to complete colorectal cancer screening when recommended by a race-concordant healthcare provider. Leveraging virtual healthcare assistants to deliver tailored screening interventions may promote adherence to colorectal cancer screening guidelines among diverse patient populations. The purpose of this pilot study is to determine the efficacy of the Agent Leveraging Empathy for eXams virtual healthcare assistant intervention to increase patient intentions to talk to their doctor about colorectal cancer screening. It also examines the influence of animation and race concordance on intentions to complete colorectal cancer screening. METHODS: White and Black adults (N=1,363) aged 50-73 years and not adherent to colorectal cancer screening guidelines were recruited from Qualtrics Panels in 2018 to participate in a 3-arm (animated virtual healthcare assistant, static virtual healthcare assistant, attention control) message design experiment. In 2020, a probit regression model was used to identify the intervention effects. RESULTS: Participants assigned to the animated virtual healthcare assistant (p<0.01) reported higher intentions to talk to their doctor about colorectal cancer screening than participants assigned to the other conditions. There was a significant effect of race concordance on colorectal cancer screening intentions but only in the static virtual healthcare assistant condition (p=0.04). Participant race, age, trust in healthcare providers, health literacy, and cancer information overload were also significant predictors of colorectal cancer screening intentions. CONCLUSIONS: Animated virtual healthcare assistants were efficacious compared with the static virtual healthcare assistant and attention control conditions. The influence of race concordance between source and participant was inconsistent across conditions. This warrants additional investigation in future studies given the potential for virtual healthcare assistant‒assisted interventions to promote colorectal cancer screening within guidelines.

Efficacy and Effectiveness of Mobile Health Technologies for Facilitating Physical Activity in Adolescents: Scoping Review.

BACKGROUND: Increasing physical activity (PA) levels in adolescents aged 12 to 18 years is associated with prevention of unhealthy weight gain and improvement in cardiovascular fitness. The widespread availability of mobile health (mHealth) and wearable devices offers self-monitoring and motivational features for increasing PA levels and improving adherence to exercise programs. OBJECTIVE: The aim of this scoping review was to identify the efficacy or effectiveness of mHealth intervention strategies for facilitating PA among adolescents aged 12 to 18 years. METHODS: We conducted a systematic search for peer-reviewed studies published between 2008 and 2018 in the following electronic databases: PubMed, Google Scholar, PsychINFO, or SportDiscus. The search terms used included mHealth or "mobile health" or apps, "physical activity" or exercise, children or adolescents or teens or "young adults" or kids, and efficacy or effectiveness. Articles published outside of the date range (July 2008 to October 2018) and non-English articles were removed before abstract review. Three reviewers assessed all abstracts against the inclusion and exclusion criteria. Any uncertainties or differences in opinion were discussed as a group. The inclusion criteria were that the studies should (1) have an mHealth component, (2) target participants aged between 12 and 18 years, (3) have results on efficacy or effectiveness, and (4) assess PA-related outcomes. Reviews, abstracts only, protocols without results, and short message service text messaging-only interventions were excluded. We also extracted potentially relevant papers from reviews. At least 2 reviewers examined all full articles for fit with the criteria and extracted data for analysis. Data extracted from selected studies included study population, study type, components of PA intervention, and PA outcome results. RESULTS: Overall, 126 articles were initially identified. Reviewers pulled 18 additional articles from excluded review papers. Only 18 articles were passed onto full review, and 16 were kept for analysis. The included studies differed in the sizes of the study populations (11-607 participants), locations of the study sites (7 countries), study setting, and study design. Overall, 5 mHealth intervention categories were identified: website, website+wearable, app, wearable+app, and website+wearable+app. The most common measures reported were subjective weekly PA (4/13) and objective daily moderate-to-vigorous PA (5/13) of the 19 different PA outcomes assessed. Furthermore, 5 of 13 studies with a control or comparison group showed a significant improvement in PA outcomes between the intervention group and the control or comparison group. Of those 5 studies, 3 permitted isolation of mHealth intervention components in the analysis. CONCLUSIONS: PA outcomes for adolescents improved over time through mHealth intervention use; however, the lack of consistency in chosen PA outcome measures, paucity of significant outcomes via between-group analyses, and the various study designs that prevent separating the effects of intervention components calls into question their true effect.

New-Onset Diabetes Educator to Educate Children and Their Caregivers About Diabetes at the Time of Diagnosis: Usability Study.

BACKGROUND: Diabetes self-management education is essential at the time of diagnosis. We developed the New-Onset Diabetes Educator (NODE), an animation-based educational web application for type 1 diabetes mellitus patients. OBJECTIVE: Our hypothesis is that NODE is a feasible, effective and user-friendly intervention in improving diabetes self-management education delivery to child/caregiver-dyads at the time of diagnosis. METHODS: We used a pragmatic parallel randomized trial design. Dyads were recruited within 48 hours of diagnosis and randomized into a NODE-enhanced diabetes self-management education or a standard diabetes self-management education group. Dyads randomized in the NODE group received the intervention on an iPad before receiving the standard diabetes self-management education with a nurse educator. The Diabetes Knowledge Test 2 assessed disease-specific knowledge pre- and postintervention in both groups, and was compared using t tests. Usability of the NODE mobile health intervention was assessed in the NODE group. RESULTS: We recruited 16 dyads (mean child age 10.75, SD 3.44). Mean Diabetes Knowledge Test 2 scores were 14.25 (SD 4.17) and 18.13 (SD 2.17) pre- and postintervention in the NODE group, and 15.50 (SD 2.67) and 17.38 (SD 2.26) in the standard diabetes self-management education group. The effect size was medium (Δ=0.56). Usability ratings of NODE were excellent. CONCLUSIONS: NODE is a feasible mobile health strategy for type 1 diabetes education. It has the potential to be an effective and scalable tool to enhance diabetes self-management education at time of diagnosis, and consequently, could lead to improved long-term clinical outcomes for patients living with the disease.

Accuracy of weight loss information in Spanish search engine results on the internet.

OBJECTIVE: To systematically assess the quality of online information related to weight loss that Spanish speakers in the U.S. are likely to access. METHODS: This study evaluated the accessibility and quality of information for websites that were identified from weight loss queries in Spanish and compared this with previously published results in English. The content was scored with respect to five dimensions: nutrition, physical activity, behavior, pharmacotherapy, and surgical recommendations. RESULTS: Sixty-six websites met eligibility criteria (21 commercial, 24 news/media, 10 blogs, 0 medical/government/university, 11 unclassified sites). Of 16 possible points, mean content quality score was 3.4 (SD = 2.0). Approximately 1.5% of sites scored greater than 8 (out of 12) on nutrition, physical activity, and behavior. Unsubstantiated claims were made on 94% of the websites. Content quality scores varied significantly by type of website (P < 0.0001) with unclassified websites scoring the highest (mean = 6.3, SD = 1.4) and blogs scoring the lowest (mean = 2.2, SD = 1.2). All content quality scores were lower for Spanish websites relative to English websites. CONCLUSIONS: Weight loss information accessed in Spanish Web searches is suboptimal and relatively worse than weight loss information accessed in English, suggesting that U.S. Spanish speakers accessing weight loss information online may be provided with incomplete and inaccurate information.

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-ß-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Ramshackle (Brwd3) promotes light-induced ubiquitylation of Drosophila Cryptochrome by DDB1-CUL4-ROC1 E3 ligase complex.

Cryptochrome (CRY) is the primary circadian photoreceptor in Drosophila. It resets the circadian clock by promoting light-induced degradation of the clock proteins Timeless and Period, as well as its own proteolysis. The E3 ligases that ubiquitylate Timeless and Period before degradation are known and it is known that Drosophila (d) CRY is degraded by the ubiquitin-proteasome system as well. To identify the E3 ligase for dCRY we screened candidates in S2 cells by RNAi. Knockdown of each of the 25 putative F-box proteins identified by bioinformatics did not attenuate the light-induced degradation of dCRY. However, knockdown of a WD40 protein, Bromodomain and WD repeat domain containing 3 (Brwd3) (CG31132/Ramshackle) caused strong attenuation of dCRY degradation following light exposure. We found that BRWD3 functions as a Damage-specific DNA binding protein 1 (DDB1)- and CULLIN (CUL)4-associated factor in a Cullin4-RING Finger E3 Ligase (CRL4) that mediates light-dependent binding of dCRY to CUL4-ROC1-DDB1-BRWD3, inducing ubiquitylation of dCRY and its light-induced degradation. Thus, this study identifies a light-activated E3 ligase complex essential for light-mediated CRY degradation in Drosophila cells.

Photoacoustic microscopy of tyrosinase reporter gene in vivo.

Photoacoustic tomography is a hybrid modality based on optical absorption excitation and ultrasonic detection. It is sensitive to melanin, one of the primary absorbers in skin. For cells that do not naturally contain melanin, melanin production can be induced by introducing the gene for tyrosinase, the primary enzyme responsible for expression of melanin in melanogenic cells. Optical resolution photoacoustic microscopy was used in the ex vivo study reported here, where the signal from transfected cells increased by more than 10 times over wild-type cells. A subsequent in vivo experiment was conducted to demonstrate the capability of photoacoustic microscopy to spectrally differentiate between tyrosinase-catalyzed melanin and various other absorbers in tissue.

Action spectrum of Drosophila cryptochrome.

Cryptochromes are a highly conserved class of UV-A/blue light photoreceptors. In Drosophila, cryptochrome is required for the normal entrainment of circadian rhythms to light dark cycles. The photocycle and molecular mechanism of animal cryptochrome photoreception are presently unknown. Drosophila cryptochrome undergoes light-dependent degradation when heterologously expressed in Schneider-2 cells. We have generated Drosophila luciferase-cryptochrome fusion proteins to more precisely monitor light-dependent cryptochrome degradation. We found that the luciferase-cryptochrome fusion protein undergoes light-dependent degradation with luciferase activity declining approximately 50% within 5 min of light exposure and approximately 85% within 1 h of light exposure. Degradation is inhibited by MG-132, consistent with a proteasomal degradation mechanism. Irradiance-response curves yield an action spectrum similar to absorption spectra for prokaryotic and eukaryotic cryptochromes with highest sensitivity in the UV-A. A luciferase-cryptochrome fusion protein lacking the terminal 15 amino acids is stably expressed in the dark but demonstrates increased sensitivity to light-induced degradation. The conferral of light-dependent degradation on a heterologous protein by fusion to cryptochrome may be a useful tool for probing protein function in cell expression systems.

Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms.

OBJECTIVE: To characterize temporal changes in mouse aortic wall gene expression associated with the development of experimental abdominal aortic aneurysms. METHODS: C57BL/6 mice underwent transient perfusion of the abdominal aorta with either elastase (n = 61) or heat-inactivated elastase as a control (n = 68). Triplicate samples of radiolabeled aortic wall complementary DNA were prepared at intervals of 0, 3, 7, 10, and 14 days, followed by hybridization to nylon microarrays (1181 genes). Autoradiographic intensity data were normalized by conversion to z scores, and differences in gene expression were defined by two-tailed z tests at a significance threshold of P < .01. RESULTS: Elastase perfusion caused a progressive increase in aortic diameter up to 14 days accompanied by transmural inflammation and destructive remodeling of the elastic media. No aneurysms occurred in the control group. Compared with healthy aorta, 336 genes exhibited significant alterations during at least 1 interval after elastase perfusion (135 at more than 1 interval and 14 at all intervals), with pronounced increases for interleukin 6, cyclin E2, interleukin 1beta, osteopontin, CD14/lipopolysaccharide receptor, P-selectin glycoprotein ligand 1, and gelatinase B/matrix metalloproteinase 9 (all >20-fold on day 3). Sixty-two genes exhibited synchronous alterations in the elastase and control groups, thus suggesting a nonspecific response. By direct comparisons between the elastase and control groups, there were 384 genes with significant differences in expression for at least 1 interval after aortic perfusion, including 234 with differential upregulation (eg, p44MAPK/ERK1, osteopontin, heat shock protein 84, hypoxia-inducible factor 1alpha, apolipoprotein E, monocyte chemotactic protein 3, MIG (monokine induced by gamma interferon), and interleukin 2 receptor gamma) and 163 with differential downregulation (eg, prothrombin, granzyme B, ataxia telangiectasia mutated, and interleukin-converting enzyme). CONCLUSIONS: Development of elastase-induced abdominal aortic aneurysms in mice is accompanied by altered aortic wall expression of genes associated with acute and chronic inflammation, matrix degradation, and vascular tissue remodeling. Knowledge of these alterations will facilitate further studies on the functional molecular mechanisms that underlie aneurysmal degeneration.

Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice.

OBJECTIVE: To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) can influence the development of experimental abdominal aortic aneurysms (AAAs). SUMMARY BACKGROUND DATA: AAAs are associated with atherosclerosis, chronic inflammation, and matrix metalloproteinase (MMP)-mediated connective tissue destruction. Because statins exert antiinflammatory activities independent of their lipid-lowering effects, these agents may help suppress aneurysmal degeneration. METHODS: C57Bl/6 wild-type and hypercholesterolemic apoE-deficient mice underwent transient perfusion of the aorta with elastase followed by subcutaneous treatment with either 2 mg/kg simvastatin per day or vehicle. Aortic diameter (AD) was measured before and 14 days after elastase perfusion. The extent of aortic dilatation (DeltaAD) was determined with AAAs defined as DeltaAD >100%. RESULTS: Wild-type mice treated with simvastatin exhibited a 21% reduction in DeltaAD and a 33% reduction in AAAs compared with vehicle-treated controls. Suppression of AAAs in simvastatin-treated mice was associated with preservation of medial elastin and vascular smooth muscle cells, as well as a relative reduction in aortic wall expression of MMP-9 and a relative increase in expression of TIMP-1. In hypercholesterolemic apoE-deficient mice, treatment with simvastatin was associated with a 26% reduction in DeltaAD and a 30% reduction in AAAs. Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice. CONCLUSIONS: Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. The mechanisms of this effect are independent of lipid-lowering and include preservation of medial elastin and smooth muscle cells, as well as altered aortic wall expression of MMPs and their inhibitors.