Mass transport, atherogenesis, and risk.
Mass transport, atherogenesis, and risk.
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质量运输、动脉粥样硬化形成和风险。
DOI：
10.1161/01.atv.7.1.88
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Fry,DL
中科院分区：
文献类型：
--
作者：
Fry,DL
如果某一特定致动脉粥样硬化分子(致动脉粥样硬化原)的局部化学活性间质浓度(化学活性)被认为是导致局部致动脉粥样硬化变化的反应系统的基本驱动力之一，那么该化学活性可被用作病变发展潜力或局部“风险”的量度。一个假定的动脉粥样硬化物质通过多层动脉壁的稳态、组合、扩散和对流传输模型被用来说明传输过程与组织屏障相互作用以确定跨壁(x轴)化学活性分布的机制[a(X)，摩尔厘米-3]。该模型被用来评估内皮间隙分数增加(内皮通透性增加)、血压升高、血清动脉粥样硬化原浓度升高、弹性内膜开窗和预先存在的内膜增厚对a(X)的影响。研究发现，动脉树上血管内皮细胞间隙面积“轻度”增加和伴随的动脉粥样硬化间质筛子形成高的a(X)，在某些情况下远高于血液的(A0)，因此即使在没有其他危险因素的情况下也是高风险的。此外，随着高血压和/或血清动脉粥样硬化原浓度的升高和/或先前存在的内膜增厚，这些部位的风险显著增加。然而，如果没有任何一种情况，即开放的内皮细胞间连接或下层间质筛选，这些其他危险因素是无效的。最后，模型的响应被证明与各种众所周知的以及令人费解的观察结果是一致的，这些观察表明运输过程可能在决定动脉粥样硬化病变的结构及其发展速度方面发挥作用。
If the local chemically-active interstitial concentration (chemical activity) of a particular atherogenic molecule (atherogen) is considered to be one of the fundamental driving forces in a system of reactions that produces an associated local atherogenic change, then the chemical activity may be used as a measure of the potential for lesion development or local "risk." A model of steady-state, combined, diffusive and convective transport of an assumed atherogen across a multilayered arterial wall was used to illustrate mechanisms by which transport processes interact with tissue barriers to determine the transmural (x axis) chemical activity distributions [a(x), mol cm-3]. The model was used to evaluate the effects of increased endothelial gap fractional area (increased endothelial permeability), elevated blood pressure, elevated serum concentration of the atherogen, internal elastica fenestration, and preexisting intimal thickening on a(x). It was found that sites along the arterial tree that are characterized by "mild" increases in endothelial gap fractional area and concomitant subjacent interstitial sieving of the atherogen developed high a(x), in some cases much higher than that (a0) of the blood, and therefore were at high risk even in the absence of other risk factors. Moreover, the risk at such sites was dramatically increased with hypertension and/or elevated serum atherogen concentration and/or preexisting intimal thickening. However, if either condition, i.e., opened endothelial intercellular junctions or subjacent interstitial sieving, was absent, these other risk factors were ineffective. Finally, the response of the model was shown to be consistent with a variety of well-known, as well as puzzling, observations suggesting that transport processes may play roles in determining both the architecture of the atherosclerotic lesion and its rate of development.