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CHA PTE R

Review of the Essential Roles of SMCs

in ATAA Biomechanics

Claudie Petit*, S. Jamaleddin Mousavi*,St ephane Avril*

*Mines Saint-Etienne, University of Lyon, INSERM, U1059 Sainbiose, Saint-Etienne, France

6.1 INTRODUCTION

Aortic aneurysms (AAs) are among the most critical cardiovascular diseases [1, 2]. Although their detection is dif-
ficult, prevention and monitoring of AA are essential as large AAs present high risks of dissection or rupture, which are
often fatal complications [2, 3]. Monitoring consists of measuring the aneurysm diameter using medical imaging
methods such as echography or CT scan [2, 3].
The present study is focused on ascending thoracic AAs (ATAAs). The risk of rupture of ATAAs is estimated clin-
ically with the maximum aneurysm diameter, which consists of considering surgical repair for ATAA diameters larger
than 5.5 cm. Other factors such as growth rate, gender, or smoking can be taken into account [2–4]. It is known that
the criterion of maximum diameter relies on statistics of the global ATAA population. On an individual basis, many
ruptures or dissections have been reported for aneurysms with diameters below the critical value [5]. Other criteria
based on biomechanics were suggested [5], but they still need to be validated clinically [6–8].
The main causes of ATAAs are summarized in Table 6.1. ATAAs are a very specific class of AA due to the partic-
ularity of the ascending thoracic aorta. First, it contains the highest density of elastic fibers of all the vasculature, and
these have to resist the mechanical fatigue induced by the wearing combination of pulsed pressure and axial stretching
repeated every cardiac beat. As elastic fibers cannot be repaired in mature tissue [9], the ascending aortic tissue is
highly prone to mechanical damage [3, 6]. Second, a major role of the contractile function in smooth muscle cells
(SMCs) is evident in the ascending aorta more than anywhere else as heterozygous mutations in the major structural
proteins or kinases controlling contraction lead to the formation of aneurysms of the ascending thoracic aorta [10].
Moreover, the outer curvature of the ascending thoracic aorta is constituted of a mix of cardiac neural crest- and second
heart field-derived SMCs, distributed over the different medial lamellar units (MLUs) (Fig. 6.1)[11]. This may be cor-
related with the observation that dilatations are more often located on the outer curvature of the ascending thoracic
aorta [12]. Third, the ascending thoracic aorta experiences very complex flow profiles, with significant alterations (vor-
tex, jet flow, eccentricity, peaks of wall shear stress) in case of bicuspid aortic valves [13–15] or aortic stenosis [15–17].
It was shown that these complex hemodynamic patterns have major interactions with the aortic wall and correlate with
local inflammatory effects or variations of oxidative stress in the aortic tissue [15, 18, 19].
Research studies dedicated to ATAA have always invoked one of the three previous particularities of the ascending
thoracic aorta to account for the intrinsic mechanism leading to the development of an ATAA, even if recent studies
tend more and more to invoke multifactorial effects. In this review, we show that all these effects converge toward a
single paradigm relying upon the crucial biomechanical role of SMCs in controlling the distribution of mechanical
stresses across the different components of the aortic wall. The chapter is organized as follows. In Section 6.2,we
introduce the basics of arterial wall biomechanics and how the stresses are distributed across its different layers.
In Section 6.3, we introduce the biomechanical active role of SMCs and its main regulators and show how this can
control the distribution of stresses across the aortic wall. In Section 6.4, we review the different pathways of SMC
mechanotransduction and their mechanisms at the cellular and tissue level in the aortic wall. Finally, we review studies
showing that SMCs tend to have a preferred homeostatic tension. We show that mechanosensing can be understood as

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