Aging, Viral Immunity and Atherosclerosis

描述（由申请人提供）：临床研究表明，衰老会增加动脉粥样硬化的风险。随着老年人数量的持续增长，老年人动脉粥样硬化的发病率将对我们的医疗资源造成沉重的负担。越来越多的人认识到炎症是支持动脉粥样硬化发展的关键病理生理机制。重要的是，实验和临床研究都提供了证据，证明微生物感染，包括病毒，加剧了动脉粥样硬化的发展。先前的研究表明，衰老会损害免疫功能，导致清除病毒的能力下降。我们实验室最近获得的R01 （R01AG028082）支持的数据表明，衰老会损害浆细胞样DCs （pDCs）的功能，而pDCs是病毒感染的关键先天传感器。这项K02应用将补充目前资助的R01，并将研究衰老如何加速动脉粥样硬化过程；特别是，它将阐明病毒感染加剧动脉粥样硬化与衰老的机制。重要的是，我们将研究基于tlr的疫苗是否可以防止随后的病毒感染并改善病毒加重的动脉粥样硬化。为了验证这些假设，我们将与两位资深血管生物学家，dr。Sessa和Tellides。因此，这个K02提案将使我能够专注于我的研究项目，并开发新的科学合作，这将有助于领导未来的项目项目，研究衰老对心血管疾病的影响。相关性（见说明）：我们社会中老年人的数量将继续增长。随着老年人患心脏病和中风的可能性增加，了解衰老是如何导致心血管疾病增加的势在必行。本研究将利用小鼠实验模型研究衰老导致心血管疾病的机制。

DESCRIPTION (provided by applicant): Clinical Studies have demonstrated that aging increases the risk of atherosclerosis. As the number of older people continues to grow, morbidity from atherosclerosis in older adults will pose a heavy burden on our health care resources. There has been a growing appreciation that inflammation is a key pathopysiological mechanism that underpins the development of atherosclerosis. Importantly, both experimental and clinical studies provide evidence that microbial infections, including viruses, exacerbate the development of atherosclerosis. Prior studies have demonstrated that aging impairs immune function and leads to a reduced ability to clear viruses. Data from our laboratory, supported by a recently acquired R01 (R01AG028082), has demonstrated that aging impairs the function of plasmacytoid DCs (pDCs), critical innate sensors of viral infection. This K02 application will complement the currently funded R01 and will examine how aging accelerates the atherosclerotic process; in particular, it will elucidate the mechanisms by which viral infections exacerbate atherosclerosis with aging. Importantly, we will examine if TLR-based vaccines protect against subsequent viral infection with aging and ameliorate virus-exacerbated atherosclerosis. In testing these hypotheses, we will collaborate with two senior vascular biologists, Drs. Sessa and Tellides. Thus, this K02 proposal will allow me to focus on my research program and develop new scientific collaborations that will be instrumental to leading a future program project on the effects of aging on cardiovascular diseases. Relevance (see instructions): The number of older people in our society will continue to grow. As older people will have an increased probability of developing heart attacks and strokes, it will be imperative to understand how aging leads to increased cardiovascular diseases. This proposal will investigate mechanisms by which aging leads to cardiovascular diseases using murine experimental models.