PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation

Atrial fibrillation (AF) is an irregular heart rhythm, characterised by chaotic atrial activation, which is promoted by remodelling. Once initiated, AF can also propagate the progression of itself in the so-called ‘‘AF begets AF’’. Several lines of investigation have shown that signalling molecules, including reactive oxygen species, angiotensin II, and phosphoinositide 3-kinases (PI3Ks), in presence or absence of cardiovascular disease risk factors, stabilise and promote AF maintenance. In particular, reduced cardiac-specific PI3K activity that is not associated with oncology is cardiotoxic and increases susceptibility to AF. Atrial-specific PI3K(p110α) transgene can cause pathological atrial enlargement. Highlighting the crucial importance of the p110α protein in a clinical problem that currently challenges the professional health care practice, in over forty (40) transgenic mouse models of AF (Table1), currently existing, of which some of the models are models of human genetic disorders, including PI3K(p110α) transgenic mouse model, over 70% of them reporting atrial size showed enlarged, greater atrial size. Individuals with minimal to severely dilated atria develop AF more likely. Left atrial diameter and volume stratification are an assessment for follow-up surveillance to detect AF. Gene therapy to reduce atrial size will be associated with a reduction in AF burden. In this overview, PI3K(p110α), a master regulator of organ size, was investigated in atrial enlargement and in physiological determinants that promote AF.