Table 2.

Role of cardiac AKAPs in physiological and in myocardial infarction. AKAP: A-kinase anchoring protein; MI: myocardial infarction; PP1/2B/2A: Protein Phosphatase 1/2B/2A; PDE: phosphodiesterase; Drp1: Dynamin Related Protein 1; AC5/6: adenylyl cyclase 5/6; PKC: Protein Kinase C; LTCC: L Type Calcium channel; cAMP: cyclic Adenosine Monophosphate; Epac 1: Exchange Protein Activated by cAMP; RyR: Ryanodine Receptor; NCX: Na/Ca exchange; HIF1α: Hypoxia Induce Factor 1α MEF2: Myocyte Enhancer Factor 2; NHERF: Na⁺/H⁺ Exchanger Regulatory factor; CaN: calcineurin; β-Ars: β-Arrestins; β2-AR: β2-Adrenergic Receptor.

AKAP	Physiological Function		MI Alteration and Therapeutic Interest
AKAP1 D-AKAP1 S-AKAP84 AKAP121 AKAP149	Dual AKAP Mitochondrial localization Anchors PP1, PP2B, PDE4, Drp1 Regulates mitochondrial dynamic Favors the phosphorylation of bad, prevents cell death	[140]	Inhibits mitochondrial fission, triggers cell survival Ubiquitination by Siah2 leads to ROS production, oxidative stress, mitochondrial dysfunction, cardiomyocytes death	[31] [151]
AKAP5 AKAP79 AKAP75 AKAP150	Type II AKAP T-tubule localization Anchors AC5 and 6, PKC, F actin, cadherin, LTCC Inhibits cAMP production Regulates LTCC mediating Ca2+ entry	[152] [153] [154]	AKAP5KO exhibits impaired Ca2+ signaling and cardiac dysfunction Reduces IKv and favors arrythmia susceptibility	[155] [156]
AKAP6 mAKAP AKAP100	Type II AKAP Outer nuclear membrane Anchors nesprin1a, AC5, Epac1, PDE4D3, RyR2, NCX, HIF1a, MEF2, kinases, PP2A and PP2B Regulates cAMP production through AC5 and PDE4D3 Regulates oxygen homeostasis through HIF1a ubiquitination	[157] [158] [159] [160]	AKAP1 inhibition induced ubiquitination of HIF1α and transcription of pro-survival genes	[160,161]
AKAP8 AKAP95	Dual AKAP (binds PKA RIIα >>> RIIβ	[162,163]	Specific AKAP8 inhibition decreases cell apoptosis	[164]
AKAP10 D-AKAP2	Dual AKAP Mitochondrial localization Anchors NHERF, Rab4 and Rab11	[165]	Polymorphism I646V increases susceptibility to MI	[166]
AKAP12 Gravin AKAP250 SSeCKS	Type II AKAP Plasma membrane, cytoskeleton or cytoplasm localization Anchors PKC, PLK1, PDE4D4, CaN, β-Ars, β2-AR β2-AR desensitization	[167] [168] [169] [170]	AKAP12KO develops apoptosis, fibrosis, oxidative stress in response to angiotensin II AKAP12 overexpression suppresses fibrosis	[171] [172]