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Mechanical Regulation of Apoptosis in the Cardiovascular System

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Abstract

Apoptosis is a highly conserved physiological process of programmed cell death which is critical for proper organism development, tissue maintenance, and overall organism homeostasis. Proper regulation of cell removal is crucial, as both excessive and reduced apoptotic rates can lead to the onset of a variety of diseases. Apoptosis can be induced in cells in response to biochemical, electrical, and mechanical stimuli. Here, we review literature on specific mechanical stimuli that regulate apoptosis and the current understanding of how mechanotransduction plays a role in apoptotic signaling. We focus on how insufficient or excessive mechanical forces may induce apoptosis in the cardiovascular system and thus contribute to cardiovascular disease. Although studies have demonstrated that a broad range of mechanical stimuli initiate and/or potentiate apoptosis, they are predominantly correlative, and no mechanisms have been established. In this review, we attempt to establish a unifying mechanism for how various mechanical stimuli initiate a single cellular response, i.e. apoptosis. We hypothesize that the cytoskeleton plays a central role in this process as it does in determining myriad cell behaviors in response to mechanical inputs. We also describe potential approaches of using mechanomedicines to treat various diseases by altering apoptotic rates in specific cells. The goal of this review is to summarize the current state of the mechanobiology field and suggest potential avenues where future research can explore.

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Figure 1
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(a–d) Images are adapted from Narula et al.96

Figure 4

(a–c) Images are adapted from Jian et al.60 (d–g) Images are adapted from Tanaka, et al.133.

Figure 5
Figure 6
Figure 7
Figure 8

Images are adapted from Cirka et al.18, and Goldblatt et al.39.

Figure 9
Figure 10

Figure is adapted from Chan et al.11

Figure 11

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Acknowledgments

This work was funding in part by Grants from the National Science Foundation (CMMI 1761432), the American Heart Association (Grant No. 14PRE18310016) to H.A.C., and the National Science Foundation IGERT (Grant No. DGE 1144804) to Z.E.G. and H.A.C.

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    Zachary E. Goldblatt, Heather A. Cirka & Kristen L. Billiar

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Goldblatt, Z.E., Cirka, H.A. & Billiar, K.L. Mechanical Regulation of Apoptosis in the Cardiovascular System. Ann Biomed Eng 49, 75–97 (2021). https://doi.org/10.1007/s10439-020-02659-x

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