Publications

Lipid accumulation in the heart is associated with obesity and diabetes mellitus and may play an important role in the pathogenesis of heart failure seen in this patient population. Stored triglycerides are synthesized by the enzyme diacylglycerol acyl transferase (DGAT). We hypothesized that forced expression of DGAT1 in the cardiac myocyte would result in increased lipid accumulation and heart dysfunction. A cardiac myocyte-selective DGAT1 transgenic mouse was created and demonstrated increased lipid accumulation in the absence of hyperglycemia, plasma dyslipidemia or differences in body weight. Over time, expression of DGAT1 in the heart resulted in the development of a significant cardiomyopathy. Echocardiography revealed diastolic dysfunction with increased early mitral inflow velocity to late mitral inflow velocity ratio and decreased deceleration time, suggesting a restrictive pattern in the transgenic mice. Moderate systolic dysfunction was also seen at 52 weeks. Histological analysis showed increased cardiac fibrosis and increased expression of procollagen type 1A, matrix metalloproteinase 2, and tissue inhibitor of matrix metalloproteinase 2 in the transgenic mice. Mitochondrial biogenesis was reduced in the transgenic hearts, as was expression of cytochrome c oxidase 1 and cytochrome c. Expression of key transcription factors important in the regulation of mitochondrial biogenesis were reduced. These findings suggest that triglyceride accumulation, in the absence of systemic metabolic derangement, results in cardiac dysfunction and decreased mitochondrial biogenesis.

BACKGROUND

Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults.

METHODS

T cell phenotyping and carotid ultrasound were assessed among 115 HIV-infected women and 43 age- and race/ethnicity-matched HIV-uninfected controls participating in the Women's Interagency HIV Study. Multivariate analyses were used to assess the association of T cell activation (CD38(+)HLA-DR(+)) and senescence (CD28(-)CD57(+)) with subclinical carotid artery disease.

RESULTS

Compared with HIV-uninfected women, frequencies of CD4(+)CD38(+)HLA-DR(+), CD8(+)CD38(+)HLA-DR(+), and CD8(+)CD28(-)CD57(+) T cells were higher among HIV-infected women, including those who achieved viral suppression while receiving antiretroviral treatment. Among HIV-infected women, adjusted for age, antiretroviral medications, and viral load, higher frequencies of activated CD4(+) and CD8(+) T cells and immunosenescent CD8(+) T cells were associated with increased prevalence of carotid artery lesions (prevalence ratio(lesions) associated with activated CD4(+) T cells, 1.6 per SD [95% confidence interval {CI}, 1.1-2.2]; P = .02; prevalence ratio(lesions) associated with activated CD8(+) T cells, 2.0 per SD [95% CI, 1.2-3.3]; P < .01; prevalence ratio(lesions) associated with senescent CD8(+) T cells, 1.9 per SD [95% CI, 1.1-3.1]; P = .01).

CONCLUSIONS

HIV-associated T cell changes are associated with subclinical carotid artery abnormalities, which may be observed even among those patients achieving viral suppression with effective antiretroviral therapy.

BACKGROUND

Separate health-related quality of life (HRQL) instruments exist for asthma and rhinitis. The Rhinasthma questionnaire, originally developed in Italian, is a unique measure designed for use where both conditions coexist.

OBJECTIVE

We sought to assess the performance and validity of a new adaptation of the Rhinasthma questionnaire for use in English-speaking populations.

METHODS

We analyzed cross-sectional data from an ongoing study of adults with asthma and rhinitis (n = 450), asthma alone (n = 75), or rhinitis alone (n = 20). Subjects were administered an English translation of the original 30-item Rhinasthma questionnaire. Health status measures simultaneously assessed include the Short Form (SF)-12, EuroQol (EQ)-5D, and Marks Asthma Quality-of-Life.

RESULTS

Variable cluster analysis of the original 30-item instrument identified 5 discrete item clusters corresponding to the following domains: nasal (5 items), eye (4 items), respiratory (5 items), activity restriction (9 items), and treatment burden (5 items). Two other items were removed because of poor item-cluster correlations. Subjects with concomitant asthma and rhinitis had greater HRQL impairment, as measured by the Rhinasthma, than subjects with either asthma or rhinitis alone. The Rhinasthma correlated significantly (P < .05) with the SF-12, EQ-5D, and Marks Asthma Quality-of-Life in the anticipated direction consistent with the underlying constructs. In multiple logistic regression, poorer Rhinasthma HRQL was associated with significantly (P < .05) increased odds of both asthma- and rhinitis-related disability even after taking into account physical health status as measured by the SF-12.

CONCLUSION

The 28-item English adaptation of Rhinasthma performs well in assessing HRQL in patients with asthma, rhinitis, or both conditions combined.