The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications

Abstract

Cardiovascular disease is the most common cause of death among diabetic patients worldwide. Hence, cardiovascular wellbeing in diabetic patients requires utmost importance in disease management. Recent studies have demonstrated that protein kinase C activation plays a vital role in the development of cardiovascular complications via its activation of mitogen-activated protein kinase (MAPK) cascades, also known as PKC-MAPK pathways. In fact, persistent hyperglycaemia in diabetic conditions contribute to preserved PKC activation mediated by excessive production of diacylglycerol (DAG) and oxidative stress. PKC-MAPK pathways are involved in several cellular responses, including enhancing oxidative stress and activating signalling pathways that lead to uncontrolled cardiac and vascular remodelling and their subsequent dysfunction. In this review, we discuss the recent discovery on the role of PKC-MAPK pathways, the mechanisms involved in the development and progression of diabetic cardiovascular complications, and their potential as therapeutic targets for cardiovascular management in diabetic patients.

β-Caryophyllene, a Dietary Phytocannabinoid, Alleviates Diabetic Cardiomyopathy in Mice by Inhibiting Oxidative Stress and Inflammation Activating Cannabinoid Type-2 Receptors

“…On the contrary, the mitogen-activated protein kinase (MAPK) pathway mediated by ERK, JNK, and p38 has been implicated in the regulation of various cellular events such as insulin resistance and inflammation . Stimulation of JNK and p38 MAPK protein kinases has a vital function in the generation of inflammatory responses .…”

“…On the contrary, the mitogen-activated protein kinase (MAPK) pathway mediated by ERK, JNK, and p38 has been implicated in the regulation of various cellular events such as insulin resistance and inflammation . Stimulation of JNK and p38 MAPK protein kinases has a vital function in the generation of inflammatory responses . Another MAPK protein kinase such as ERK becomes phosphorylated and activated by MEK, and activated ERK1/2 has a critical effect in inflammation since NF-κB has been known as its downstream target and recognized to promote IL-1β signaling .…”

“…66 Stimulation of JNK and p38 MAPK protein kinases has a vital function in the generation of inflammatory responses. 66 Another MAPK protein kinase such as ERK becomes phosphorylated and activated by MEK, and activated ERK1/2 has a critical effect in inflammation since NF-κB has been known as its downstream target and recognized to promote IL-1β signaling. 67 The enhancement of p38 MAPK and JNK is proved from the overexpression of p38 MAPK and JNK proteins in the heart of DCM mice, while treating DCM mice with BCP has attenuated the DCM-mediated stimulation of p38 MAPK and JNK pathways indicated by the downregulated protein expression of p38 MAPK and JNK.…”

Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review

“…The signaling pathway that was found to be responsible for the progression of heart failure mediated by inflammation response and apoptotic factors could be related to the mitogen-activated protein kinase (MAPK) pathway, as summarized in Figure 1 [ 21 , 22 , 23 ]. Persistent dyslipidemia, hyperglycemia, and hypertension can significantly drive reactive oxygen species (ROS) production and set off inflammatory responses and apoptosis signalling pathways [ 24 , 25 ].…”

“…Dead cardiomyocytes are replaced with fibrotic tissue deposition, including collagen I and collagen III, in the extracellular matrix (ECM) space. Due to the characteristics of stiff collagen tissue, the heart shows an abnormality in its functioning, such as reduced force in contractility as well as myocardial hypertrophy [ 22 ]. Uncontrolled myocardial fibrosis leads to the onset of diastolic and systolic dysfunction, which in turn leads to the progression of heart failure.…”