Tanaka Leonardo Y, Laurindo Francisco R M
Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, Av. Enéas Carvalho Aguiar, 44, Annex II, 9th Floor, São Paulo CEP 05403-000, Brazil.
Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, Av. Enéas Carvalho Aguiar, 44, Annex II, 9th Floor, São Paulo CEP 05403-000, Brazil.
Free Radic Biol Med. 2017 Aug;109:11-21. doi: 10.1016/j.freeradbiomed.2017.01.025. Epub 2017 Jan 18.
Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases.
血管重塑，即整个血管的结构重塑，在（病理）生理学中决定管腔口径。在此，我们综述血管重塑的潜在机制，重点关注氧化还原调节。首先，我们讨论令人困惑的术语，并聚焦狭义的重塑。其次，我们基于张力稳态作为设定点调节器的概念提出一种力学生物学重塑范式。我们首先将剪切介导的模型作为由高度氧化还原敏感的内皮功能密切主导的重塑原型进行重点讨论。更详细的讨论聚焦于机械传感器、整合素、细胞外基质、细胞骨架和炎症途径，它们是将张力稳态与氧化还原调节耦合的潜在机制。对与动脉粥样硬化和损伤修复相关的重塑的进一步讨论突出了氧化还原血管反应的重要方面。虽然新生内膜形成对抗氧化剂未表现出一致的反应性，但血管重塑的反应性更明显，这表明尽管存在多级氧化还原信号通路，但整个血管存在协调反应。在可能协调氧化还原途径的机制中，我们讨论超氧化物歧化酶活性和细胞外蛋白质二硫键异构酶的作用。然后我们讨论动脉瘤的氧化还原调节，这是扩张性重塑的一个特殊情况。我们提出血管重塑的氧化还原调节可能反映（1）重塑病理生理学由特别氧化还原敏感的细胞类型主导，例如内皮细胞；（2）氧化还原途径在器官水平上跨不同细胞和无细胞结构在时间和空间上是协调的；或（3）张力稳态设定点与氧化还原信号密切相关。本文讨论的力学生物学/氧化还原模型可为更好地理解重塑提供基础，并有助于阐明常见难治性疾病的潜在机制。
