And the band played on: persistent fibrosis after unbanding reveals sex-dependent differences in rats.
And the band played on: persistent fibrosis after unbanding reveals sex-dependent differences in rats.
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束带继续发挥作用：解带后的持续纤维化揭示了大鼠的性别依赖性差异。
DOI：
10.1152/ajpheart.00327.2022
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Bradshaw,AmyD
中科院分区：
文献类型：
--
作者：
Zile,MichaelR;Bradshaw,AmyD
Ruppert等人的手稿描述了在大鼠模型中缓解压力超负荷（PO）后心脏重塑的性别依赖性差异27，在该模型中，PO通过主动脉束带诱导28，然后通过移除束带缓解。患者对PO反应的性别依赖性29的前景已经取得进展[1]，然而，男性与女性重塑诱导和/或逆转的明确机制30特征还不完整。值得注意的是，人类心脏病的复杂性和频繁相关的共病使得仅对性别依赖变量进行分类有点挑战性。然而，彼得罗夫及其同事的研究，如Ruppert等人所指出的，支持34的概念，即男性与女性对PO的反应和缓解可能存在差异，其中一些研究表明，女性在主动脉瓣置换术后表现出更大的适应性36重塑，纤维化减少[2]。在Ruppert等人提出的研究中，使用主动脉结扎和解除结扎的大鼠PO模型在一定程度上降低了患者中存在的共病状况的复杂性，并允许更清楚地检查动物模型中PO诱导的肥大的进展和消退的响应性依赖性差异。41 42 Ruppert等人报告称，雄性和雌性大鼠对PO的反应相似，在结扎6周时心脏功能的肥大43反应和适应方面，而在12周时，雄性44与雌性大鼠相比表现出PO带来的更严重的缺陷。作者提出的一点是，研究中使用的幼年雄性和雌性大鼠的体型差异相当大。因此，基于主动脉的解剖尺寸的差异，可以预测通过绑扎产生的PO程度（因为在两种性别中使用相同尺寸的针47）在雄性大鼠中产生显著更高的压力梯度和48生长刺激。虽然这49差异负荷并没有导致左心室（LV）结构和功能的性别差异在50 6周的主动脉结扎，这并不奇怪，一个差异PO（独立于性别）将导致LV结构和功能的差异在一个较长的时间带。据我们所知，人类的身体（和主动脉）大小是否以及在多大程度上也可能导致心脏重塑中的性别依赖性差异，也是相对未探索的。54 55
The manuscript by Ruppert et al. describes sex-dependent differences in cardiac remodeling 27 following alleviation of pressure overload (PO) in a rat model in which PO is induced through 28 aortic banding and then relieved by removal of the band. The prospect of sex-dependent 29 responses to PO in patients has been advanced [1], however a definitive mechanistic 30 characterization of induction and/or reversal of remodeling in men versus women is 31 incomplete. Notably, the complexity of human cardiac disease and the frequently associated 32 co-morbidities makes the classification of sex-dependent variables alone somewhat 33 challenging. However, studies by Petrov and colleagues, as noted in Ruppert et al., support the 34 concept that a differential response to, and alleviation of, PO might be present in men versus 35 women wherein some studies have shown that women demonstrate greater adaptive 36 remodeling with diminished fibrosis in response to aortic valve replacement [2]. In the studies 37 presented by Ruppert et al., the rat PO model using aortic banding and unbanding reduces to 38 some degree the complexity in terms of co-morbid conditions present in patients and allows for 39 a clearer examination of sex-dependent differences in response to progression and regression 40 of PO-induced hypertrophy in an animal model. 41 42Ruppert et al. report that male and female rats respond similarly to PO in terms of hypertrophic 43 response and adaptions in cardiac function at 6 weeks of banding, whereas at 12 weeks, males 44 demonstrate more severe deficits brought upon by PO in comparison to female rats. A point 45 raised by the authors is the considerable body size difference in juvenile male and female rats 46 used in the study. As such, the degree of PO produced by banding (as the same sized needle 47 was used in both sexes), would be predicted to yield a significantly higher pressure gradient and 48 growth stimulus in the male rats based on differences in anatomical size of the aorta. While this 49 differential load did not result in sex differences in left ventricular (LV) structure and function at 50 6 weeks of aortic banding, it is not surprising that a differential PO (independent of sex) would 51 result in differences in LV structure and function over a longer duration of banding. Whether 52 and to what extent body (and aorta) size in humans might also contribute to sex-dependent 53 differences in cardiac remodeling, to our knowledge, is also relatively unexplored. 54 55