Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats.

Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of CD47, has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking CD47 will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR. Isolated coronary arterioles from young (4 mo) or old (24 mo) female Fischer 344 rats were challenged with the NO donor, DEA-NONO-ate (1 × 10(-7) to 1 × 10(-4) M), and vessel relaxation and O2 (-) production was measured before and after Thbs-1, αCD47, and/or Tempol and catalase exposure. In vivo CFR was determined in anesthetized rats (1-3% isoflurane-balance O2) via injected microspheres following control IgG or αCD47 treatment (45 min). Isolated coronary arterioles from young and old rats relax similarly to exogenous NO, but addition of 2.2 nM Thbs-1 inhibited NO-mediated vasodilation by 24% in old rats, whereas young vessels were unaffected. Thbs-1 increased O2 (-) production in coronary arterioles from rats of both ages, but this was exaggerated in old rats. The addition of CD47 blocking antibody completely restored NO-dependent vasodilation in isolated arterioles from aged rats and attenuated O2 (-) production. Furthermore, αCD47 treatment increased CFR from 9.6 ± 9.3 (IgG) to 84.0 ± 23% in the left ventricle in intact, aged animals. These findings suggest that the influence of Thbs-1 and CD47 on coronary perfusion increases with aging and may be therapeutically targeted to reverse coronary microvascular dysfunction.

Ambient and Emission Trends of Toxic Air Contaminants in California.

After initiating a toxic air contaminant (TAC) identification and control program in 1984, the California Air Resources Board adopted regulations to reduce TAC emissions from cars, trucks, stationary sources, and consumer products. This study quantifies ambient concentration and emission trends for the period 1990-2012 for seven TACs that are responsible for most of the known cancer risk associated with airborne exposure in California. Of these seven, diesel particulate matter (DPM) is the most important; however DPM is not measured directly. Based on a novel surrogate method, DPM concentrations declined 68%, even though the state's population increased 31%, diesel vehicle-miles-traveled increased 81%, and the gross state product (GSP) increased 74%. Based on monitoring data, concentrations of benzene, 1,3-butadiene, perchloroethylene, and hexavalent chromium declined 88-94%. Also, the ambient and emissions trends for each of these four TACs were similar. Furthermore, these declines generally occurred earlier in California than elsewhere. However, formaldehyde and acetaldehyde, which are formed in the air photochemically from volatile organic compounds (VOCs), declined only 20-21%. The collective cancer risk from exposure to these seven reviewed TACs declined 76%. Significant reduction in cancer risk to California residents from implementation of air toxics controls (especially for DPM) is expected to continue.

Day-of-week patterns in toxic air contaminants in southern California.

Day-of-week mean ambient concentrations were computed for six high-cancer-risk toxic air contaminants (TACs): 1,3-butadiene, benzene, acetaldehyde, formaldehyde, carbon tetrachloride (CCl4), and perchloroethylene. Data from six urban sites in southern California, from 1989 through 2001, were analyzed. Graphical displays were used to search for repeated patterns. Benzene and 1,3-butadiene, emitted mainly by mobile sources, exhibit distinctly lower concentrations on Sundays and slightly lower concentrations on Saturdays and Wednesdays. Acetaldehyde and formaldehyde show some trace of a weekly pattern similar to that of benzene and 1,3-butadiene, but the pattern is not strongly marked. Perchloroethylene, used primarily as a dry-cleaning solvent, is also distinctly lower on Sundays. CCl4 does not show a day-of-week pattern.