Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.
Am J Physiol Heart Circ Physiol. 2011 May;300(5):H1595-601. doi: 10.1152/ajpheart.01253.2010. Epub 2011 Feb 25.
The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Göttingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) μg/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals {769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-971.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.
在动脉粥样硬化中，感染与传统心血管危险因素的协同作用备受争议。我们假设冠状动脉损伤与感染复发和病原体负担相关，并且会因高胆固醇血症而进一步加重。将 42 头哥廷根小型猪分为重复经气管内接种 PBS、肺炎衣原体（Cpn）或 Cpn 和流感病毒，分别在 8、11 和 14 周龄时进行接种。动物分为标准饮食组或 2%胆固醇饮食（高胆固醇饮食）组。在 19 周龄时，对猪进行体内乙酰胆碱（ACh）和腺苷诱导的冠状动脉血管舒缩反应评估，并采集血液和组织样本。采用非参数检验比较各组间差异。在高胆固醇饮食组中，与未感染动物相比，感染动物的总胆固醇/高密度脂蛋白胆固醇显著升高[3.13（2.17-3.38）比 2.03（1.53-2.41），P=0.01]。感染动物的 C 反应蛋白（CRP）升高[10.60（4.96-18.00）比未感染动物的 2.47（1.44-3.01）μg/ml，P<0.01]，但单感染和混合感染组间无显著差异。在混合感染组中，与标准饮食组相比，高胆固醇饮食组的 CRP 和触珠蛋白均降低（P<0.05）。混合感染动物对 ACh 的血管收缩反应最为显著[769.3（594-1,129）cm；P=0.03 比未感染[342（309-455）cm]和 P=0.07 比单感染[415（252.5-971.8）cm]）]。在单感染动物中，与 CRP 相似，高胆固醇饮食组的血管收缩反应也呈降低趋势（P=0.08）。仔猪的混合感染似乎与更明显的冠状动脉毒蕈碱血管舒缩功能障碍相关。在单感染动物中，高胆固醇饮食似乎减轻了感染引起的冠状动脉功能障碍和全身炎症。
