Mechanobiology in cardiac physiology and diseases

Abstract

Mechanosensitivity is essential for heart function just as for all other cells and organs in the body, and it is involved in both normal physiology and diseases processes of the cardiovascular system. In this review, we have outlined the relationship between mechanosensitivity and heart physiology, including the Frank-Starling law of the heart and mechanoelectric feedback. We then focused on molecules involved in mechanotransduction, particularly mechanosensitive ion channels. We have also discussed the involvement of mechanosensitivity in heart diseases, such as arrhythmias, hypertrophy and ischaemic heart disease. Finally, mechanobiology in cardiogenesis is described with regard to regenerative medicine.

Fig. 1

mRNA expressions of mechanosensitive ion channels determined by quantitative RT-PCR. Total RNA samples for liver, brain, thymus, heart, lung, spleen, testicle, ovary and kidney were obtained from 7–8 weeks old Sprague–Dawley rats. Total RNA sample for the embryo was obtained from midterm embryos of Sprague–Dawley rats. These RNA samples were purchased from Ambion. A total RNA sample for the rat ventricular cardiomyocyte cell line H9c2 was also obtained. TaqMan PCR primers were used for TRPA1, TRPC6, TRPM7, TRPV2, ASIC3 and TREK-1 channels' mRNAs. 18S ribosomal RNA was used as an internal control. Relative mRNA levels were calculated using ΔCt values (2∧(40 − ΔCt)) for each PCR run. Finally, the relative mRNA level was normalized to that of the embryo. All data are for three technical replicates.

Fig. 2

Structure of mechanosensitive ion channels. Upper panels: top views, lower panels: side views. (A) Opening of the bacterial mechanosensitive channel of small conductance (MscS, PDB accession number: 2OAU) in response to lipid bilayer stretch obtained by coarse-grained molecular dynamics simulation. MscS channel is embedded in lipid bilayers consisting of palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylethanolamine (POPE) lipids, which are shown in stick representation. The simulation box is filled with water molecules. Duration after applying a bilayer stretch is indicated in nanoseconds. Note that the channel's pore enlarges over time. (B) Three-dimensional crystal structure of mammalian Kv1.2 channel (PDB accession number: 3LUT) that putatively possesses mechanosensitivity.