Obesity and
cardiovascular diseases are worldwide public health issues. In this review, we discussed the participation of ROCK
protein in
cardiac hypertrophy, mainly through the modulation of
leptin and
insulin signaling pathways.
Leptin plays a role in
cardiovascular disease development and, through the Rho-associated
protein kinase (ROCK), promotes
cardiac hypertrophy. ROCK
protein, is regulated by small
Rho-GTPases and has two
isoforms with high homology. ROCK is able to activate the MAP
kinase (MAPK) pathway and modulate
insulin signaling in the heart, participating in
cardiac hypertrophy development of concentric and eccentric left ventricle growth. Although different types of stimulus can lead to morphologically antagonistic heart growth, physical exercise promotes improvements in hemodynamic function, emerging as a promising non-pharmacological tool to improve overall health.
Leptin can activate ROCK in a pathological way, increasing MAPK activity and decreasing
insulin signaling via
insulin receptor substrate 1 (IRS1)
serine 307 residue phosphorylation,
phosphatase and
tensin homolog, and
protein kinase Cβ2. In turn, physical exercise decreases
leptin levels and positively modulates
insulin signaling as well as increases ROCK-dependent IRS1 (Ser632/635) phosphorylation, improving
phosphatidylinositol 3-kinase/
protein kinase B axis and promoting physiologic heart growth. Currently, there is a lack of studies about differences in ROCK
isoforms, especially during exercise and/or
obesity. However, the understanding of its
biological function and the complex mechanism underlying the distinct types of
cardiac hypertrophy development can be a useful tool in the improvement and treatment of cardiovascular outcomes.