PI3Kγ Inhibition Protects Against Diabetic Cardiomyopathy in Mice

Maffei, Angelo; Cifelli, Giuseppe; Carnevale, Raimondo; Iacobucci, Roberta; Pallante, Fabio; Fardella, Valentina; Fardella, Stefania; Hirsch, Emilio; Lembo, Giuseppe; Carnevale, Daniela

doi:10.1016/j.rec.2016.04.034

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…The PI3Kγ-PKA-PDE complex also operates in a negative feedback loop, as PDE antagonizes β-AR activation of PKA [100,105]. Thus, along with studies showing that adoptive transfer of PI3Kγ KO bone marrow limits fibrosis and left-ventricular dilatation after aortic constriction [100], these studies point to PI3Kγ as a potential drug target in the treatment of heart failure in the context of pressure overload or diabetes [162,163,164,165].…”

Section: Biological Functions Of Pi3kγmentioning

confidence: 99%

Function, Regulation and Biological Roles of PI3Kγ Variants

Nürnberg

Beer‐Hammer

2019

Biomolecules

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Phosphatidylinositide 3-kinase (PI3K) γ is the only class IB PI3K member playing significant roles in the G-protein-dependent regulation of cell signaling in health and disease. Originally found in the immune system, increasing evidence suggest a wide array of functions in the whole organism. PI3Kγ occur as two different heterodimeric variants: PI3Kγ (p87) and PI3Kγ (p101), which share the same p110γ catalytic subunit but differ in their associated non-catalytic subunit. Here we concentrate on specific PI3Kγ features including its regulation and biological functions. In particular, the roles of its non-catalytic subunits serving as the main regulators determining specificity of class IB PI3Kγ enzymes are highlighted.

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Section: Biological Functions Of Pi3kγmentioning

confidence: 99%

Function, Regulation and Biological Roles of PI3Kγ Variants

Nürnberg

Beer‐Hammer

2019

Biomolecules

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“…In our laboratory, we found that a novel molecule, GE21, blocks the kinase-dependent signaling of PI3Kγ and has an antihypertensive effect in mice [16]. More recently, we have described that GE21 also has a protective functional role in diabetic cardiomyopathy, associated to a decrease in inflammation and fibrosis [27]. GE21 administrated in a dose-dependent manner is able to preserve cardiac function.…”

Section: Discussionmentioning

confidence: 99%

“…GE21 administrated in a dose-dependent manner is able to preserve cardiac function. The possibility to further test the pharmacological inhibition of PI3Kγ signaling to approach immune mechanisms in hypertension is the translational step forward that could contribute to the growing research area for therapeutic applications of PI3Kγ inhibitors [16,27,64]. …”

Section: Discussionmentioning

confidence: 99%

“…Recently, we asserted the importance of their kinase-independent activity in the integrity of synaptic plasticity and noradrenergic neurons transmission of locus coeruleus (LC), providing an unpredictable role for PI3Kγ in the neuronal excitability of LC [56]. Changes in PI3Kγ expression and modulations of the downstream pathway have been investigated as potential therapeutic targets in several pathologies affecting the vascular system, the neuronal system, and, more interestingly, immune disorders [9,25,27,57,58]. …”

Section: Pi3kγ: a Focus On Their Signaling Pathway In Cardiovasculmentioning

confidence: 99%

“…The genetic ablation of the p110γ subunit or that carry a kinase-death form of PI3Kγ allows for the dissection of molecular mechanisms undergoing immune cell activation in cardiovascular diseases [16,17,27]. In inflamed lesions, p110γ is required for the activation of Akt pathway kinase-dependent in macrophages in response to angiotensin II both in vitro and in vivo, suggesting a possible target to fight atherosclerosis in mice [26,59].…”

Section: Pi3kγ: a Focus On Their Signaling Pathway In Cardiovasculmentioning

confidence: 99%

See 2 more Smart Citations

The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation

Perrotta

Lembo

Carnevale

2016

IJMS

Self Cite

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PI3Kγ is a multifaceted protein, crucially involved in cardiovascular and immune systems. Several studies described the biological and physiological functions of this enzyme in the regulation of cardiovascular system, while others stressed its role in the modulation of immunity. Although PI3Kγ has been historically investigated for its role in leukocytes, the last decade of research also dedicated efforts to explore its functions in the cardiovascular system. In this review, we report an overview recapitulating how PI3Kγ signaling participates in the regulation of vascular functions involved in blood pressure regulation. Moreover, we also summarize the main functions of PI3Kγ in immune responses that could be potentially important in the interaction with the cardiovascular system. Considering that vascular and immune mechanisms are increasingly emerging as intertwining players in hypertension, PI3Kγ could be an intriguing pathway acting on both sides. The availability of specific inhibitors introduces a perspective of further translational research and clinical approaches that could be exploited in hypertension.

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Matrine improves diabetic cardiomyopathy through TGF‐β‐induced protein kinase RNA‐like endoplasmic reticulum kinase signaling pathway

Hou

Zhang

Dong

et al. 2019

J of Cellular Biochemistry

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Background: Matrine might play a vital role in cardiovascular diseases progression and treatment.Objectives: We aimed to explore the protective effects and potential mechanism of matrine against diabetic cardiomyopathy (DCM) in rat model.Method: A rat model of DCM was induced by streptozotocin, which were then divided into two groups and treated with matrine. Inflammatory cytokines were investigated in serum and myocardial cells after matrine administration. The effects of matrine on cardiac reactive oxygen species (ROS) generation, Malondialdehyde (MDA) levels, and Glutathione peroxidase (GPx), PPARγ1 activity were detected in myocardial cells. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway in endoplasmic reticulum stress was studied to elaborated protective effects of matrine in DCM rat by Western blot analysis. Fasting blood glucose and hemodynamic parameters were analyzed after treatment with matrine.

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PI3Kγ Inhibition Protects Against Diabetic Cardiomyopathy in Mice

Cited by 7 publications

References 22 publications

Function, Regulation and Biological Roles of PI3Kγ Variants

Function, Regulation and Biological Roles of PI3Kγ Variants

The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation

Matrine improves diabetic cardiomyopathy through TGF‐β‐induced protein kinase RNA‐like endoplasmic reticulum kinase signaling pathway

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