Lysosomal dysfunction in diabetic cardiomyopathy

Abstract

Diabetes is a major risk factor for a variety of cardiovascular complications, while diabetic cardiomyopathy, a disease specific to the myocardium independent of vascular lesions, is an important causative factor for increased risk of heart failure and mortality in diabetic populations. Lysosomes have long been recognized as intracellular trash bags and recycling facilities. However, recent studies have revealed that lysosomes are sophisticated signaling hubs that play remarkably diverse roles in adapting cell metabolism to an ever-changing environment. Despite advances in our understanding of the physiological roles of lysosomes, the events leading to lysosomal dysfunction and how they relate to the overall pathophysiology of the diabetic heart remain unclear and are under intense investigation. In this review, we summarize recent advances regarding lysosomal injury and its roles in diabetic cardiomyopathy.

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer

“…LSDs constitute a rare group of metabolic disorders stemming from inherited mutations in genes encoding proteins crucial for lysosomal homeostasis, including lysosomal hydrolases or membrane proteins [ 79 ]. Beyond LSDs, numerous diseases such as cancer, obesity, diabetes, neurodegenerative diseases, and cardiovascular diseases have been shown to exhibit close correlations with lysosomal alterations and dysfunction [ 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. This review delves into obesity and cancer, exploring their lysosomal changes and dysfunction to establish a foundation for the subsequent selection of targeted therapeutic strategies.…”

Decreasing in Lysine Reflect Lysosomal Dysfunction and Accumulated Phenylalanine which Connected to WMH and CVD and Both of Phenylketonuria and Calcifications where N-Acetylcysteine Prevent Organs Failure

“…So, it's clear that increasing in hypertrophy is related to decreasing in lysosomes functions (not related to mitochondria), and specifically connected to decreasing in atpase function which produced by lysine that necessary to activated proper lysosomal digestion through activating lysine phosphorylation and lysine acetylation which necessary to activate E coli functions. And, Lysosomal dysfunction appear in diabetic cardiomyopathy [187]. And positively, Lysine is the most effective amino acid for activating all of ATPase, GTPase, and lysosomes, and E coli functions, where ATPase necessary for activating lysine Phosphorylation for activating lysosome digestion, followed by activating E coli through activating Phe hydroxylase production, while GTPase necessary for activating mitochondrial repairs, which act on proinflammation and cholesterol for activating estrogen production and activating the NR4As pathway which activate all of Oxytocin, Nrf2 followed by Ang2-AT2 and VEGF-A production and then followed by activating heme oxygenase and anti-inflammatory growth and processes, that prevent LV-hypertrophy, and prevent coronary calcification.…”

“…That the digestion of polymers and cholesterol by lysosome will enhance full protection to kidney from polymers toxicity and damages. Also, Lysosomal dysfunction and altered activities of lysosomal cathepsins have been observed in the diabetic heart [209]. Also, Lysine functions slow down diabetic nephropathy through activating E coli and mitochondrial function followed by activating dopamine followed by activating estrogen and GC-beta through activating NR4As pathway which activate oxitocin and Nrf2 production.…”

Vascular Progenitor Cells: From Cancer to Tissue Repair

“…The organization of the vascular wall is well structured and consists of three different main functional layers: the intima, a single layer of endothelial cells, which provides an interface between blood and smooth muscle and contains vascular stem cells which are CD34 and c-kit-positive; the media, including smooth muscle cells, collagen and elastin; and the adventitia composed of undifferentiated dendritic cells, connective tissue, vasa vasorum and other cells including fibroblasts, pericytes, and cells CD34, Sca-1, c-kit, NG2 and GII1-positive. This well-organized vascular structure can deal with injuries that are often caused by several acute and chronic diseases including hypertension [ 2 ], atherosclerosis [ 3 ], diabetes [ 4 , 5 ], trauma [ 6 ], occlusions [ 7 ], hypoxia [ 8 ], primary cancerous lesions, and metastases [ 9 ] as well as catheter interventions [ 10 , 11 ].…”