Publications

BACKGROUND

A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte in an effort to better understand the role of vitamin D in regulating myocyte structure and function.

METHODS AND RESULTS

Targeted deletion of the exon 4 coding sequence in the VDR gene resulted in an increase in myocyte size and left ventricular weight/body weight versus controls both at baseline and following a 7-day infusion of isoproterenol. There was no increase in interstitial fibrosis. These knockout mice demonstrated a reduction in end-diastolic and end-systolic volume by echocardiography, activation of the fetal gene program (ie, increased atrial natriuretic peptide and alpha skeletal actin gene expression), and increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a direct downstream target of calcineurin/nuclear factor of activated T cell signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1 gene promoter activity.

CONCLUSIONS

Collectively, these studies demonstrate that the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in the heart. This appears to involve, at least in part, suppression of the prohypertrophic calcineurin/NFAT/MCIP1 pathway. These studies identify a potential mechanism to account for the reported beneficial effects of vitamin D in the cardiovascular system.

BACKGROUND

Sudden cardiac death is the leading cause of on-duty death in United States firefighters. Accurately assessing cardiopulmonary capacity is critical to preventing, or reducing, cardiovascular events in this population.

METHODS

A total of 83 male firefighters performed Wellness-Fitness Initiative (WFI) maximal exercise treadmill tests and direct peak VO2 assessments to volitional fatigue. Of the 83, 63 completed WFI sub-maximal exercise treadmill tests for comparison to directly measured peak VO2 and historical estimations.

RESULTS

Maximal heart rates were overestimated by the traditional 220-age equation by about 5 beats per minute (p < .001). Peak VO2 was overestimated by the WFI maximal exercise treadmill and the historical WFI sub-maximal estimation by ~ 1MET and ~ 2 METs, respectively (p < 0.001). The revised 2008 WFI sub-maximal treadmill estimation was found to accurately estimate peak VO2 when compared to directly measured peak VO2.

CONCLUSION

Accurate assessment of cardiopulmonary capacity is critical in determining appropriate duty assignments, and identification of potential cardiovascular problems, for firefighters. Estimation of cardiopulmonary fitness improves using the revised 2008 WFI sub-maximal equation.