PI3K signaling in arterial diseases: Non redundant functions of the PI3K isoforms

Area of Science:

• Cardiovascular biology and immunology
• Molecular and cellular mechanisms of arterial disease

Background:

• Cardiovascular diseases, including atherosclerosis, restenosis, and thrombotic complications, are leading global causes of mortality.
• Arterial pathologies arise from complex interactions between immune and arterial cells, driving inflammatory and fibroproliferative responses.
• Phosphoinositide 3-kinase (PI3K) signaling is increasingly recognized for its role in these cellular processes.

Purpose of the Study:

• To review the diverse functions of phosphoinositide 3-kinase (PI3K) isoforms in cardiovascular disease.
• To elucidate the specific roles of different PI3K isoforms in immune and arterial cells within the context of arterial pathologies.
• To identify potential PI3K isoform targets for future therapeutic strategies in treating and preventing arterial diseases.

Main Methods:

• Literature review focusing on PI3K isoform functions in cardiovascular and arterial cells.
• Analysis of PI3K isoform expression, activation, and subcellular localization.
• Synthesis of current understanding regarding PI3K's protective or detrimental effects in arterial disease models.

Main Results:

• PI3K family comprises 8 members across classes I, II, and III, with distinct substrate specificities.
• PI3K isoforms exhibit non-redundant functions due to differential expression, activation, and localization.
• Specific PI3K isoforms are implicated in both protective and deleterious effects within immune and arterial cells.

Conclusions:

• Targeting specific PI3K isoforms holds promise for novel therapeutic interventions in cardiovascular diseases.
• Further research is needed to precisely delineate the roles of each PI3K isoform in arterial disease pathogenesis.
• Selective inhibition or activation of PI3K isoforms may offer a strategy to manage atherosclerosis and its complications.