Statin Effects on Vascular Calcification: Microarchitectural Changes in Aortic Calcium Deposits in Aged Hyperlipidemic Mice.

[Figure: see text].

Changes in microarchitecture of atherosclerotic calcification assessed by 18F-NaF PET and CT after a progressive exercise regimen in hyperlipidemic mice.

BACKGROUND: Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology. METHODS: To test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF µPET/µCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry. RESULTS: Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold. CONCLUSION: These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Serotonin receptor type 2B activation augments TNF-α-induced matrix mineralization in murine valvular interstitial cells.

Calcification, fibrosis, and chronic inflammation are the predominant features of calcific aortic valve disease, a life-threatening condition. Drugs that induce serotonin (5-hydroxytryptamine [5-HT]) are known to damage valves, and activated platelets, which carry peripheral serotonin, are known to promote calcific aortic valve stenosis. However, the role of 5-HT in valve leaflet pathology is not known. We tested whether serotonin mediates inflammation-induced matrix mineralization in valve cells. Real-time reverse transcription-polymerase chain reaction analysis showed that murine aortic valve interstitial cells (VICs) expressed both serotonin receptor types 2A and 2B (Htr2a and Htr2b). Although Htr2a expression was greater at baseline, Htr2b expression was induced several-fold more than Htr2a in response to the pro-calcific tumor necrosis factor-α (TNF-α) treatment. 5-HT also augmented TNF-α-induced osteoblastic differentiation and matrix mineralization of VIC, but 5-HT alone had no effects. Inhibition of serotonin receptor type 2B, using specific inhibitors or lentiviral knockdown in VIC, attenuated 5-HT effects on TNF-α-induced osteoblastic differentiation and mineralization. 5-HT treatment also augmented TNF-α-induced matrix metalloproteinase-3 expression, which was also attenuated by Htr2b knockdown. Htr2b expression in aortic roots and serum levels of peripheral 5-HT were also greater in the hyperlipidemic Apoe-/- mice than in control normolipemic mice. These findings suggest a new role for serotonin signaling in inflammation-induced calcific valvulopathy.

Surveillance programs for chronic viral hepatitis in three health departments.

Although chronic hepatitis B and chronic hepatitis C are diseases of public health importance, only a few health departments nationally have chronic viral hepatitis under surveillance; these programs rely primarily on direct reporting by medical laboratories. We conducted an evaluation to determine if lessons from these programs can guide other health departments. Between December 2002 and February 2003, we visited the Connecticut Department of Public Health, the Multnomah County Health Department in Portland, Oregon, and the Minnesota Department of Health to determine the capacity of their chronic hepatitis registries to monitor trends and provide case management. We found that the registries facilitated investigations of potentially acute cases by identifying previously known infections, and aided prevention planning by pinpointing areas where viral hepatitis was being diagnosed. For chronic cases, case management (defined as the process of ensuring that infected individuals and their partners receive medical evaluation, counseling, vaccination, and referral to specialists for treatment when indicated) was provided for hepatitis B in Multnomah County, but was limited in other programs; barriers included resource constraints, difficulties confirming chronic infection, and privacy concerns. Finding innovative ways to overcome these barriers and improve case management is important if chronic hepatitis surveillance is to realize its full potential.

An epidemiologic summary of the hepatitis C epidemic in Minnesota.

Hepatitis C virus (HCV) infection has been described as a "silent epidemic" because the majority of HCV cases are clinically asymptomatic. This presents challenges in identification and diagnosis of HCV infection. Between 1990 and 2001, the Minnesota Department of Health received 16,913 reports of HCV enzyme immunoassay (EIA) positive cases, which represent the tip of the HCV prevalence iceberg. The most commonly identified risk factor associated with HCV infection is intravenous drug use (IDU). Among cases of HCV infection in Minnesota, 52% (2,760) of those who had reported risk-factor information reported history of IDU. Nationally, the number of new cases of acute infection is declining, but the number of persons with HCV infection is sizeable. Morbidity and mortality due to HCV-related liver disease is expected to increase greatly in the next decade. A coordinated effort between the public and private health systems will be necessary to address issues that affect the HCV-positive community.