Functional relevance of genetic variations of endothelial nitric oxide synthase and vascular endothelial growth factor in diabetic coronary microvessel dysfunction

Abstract

SUMMARY1. The prevalence of type 1 diabetes (T1D) is increasing worldwide and is associated with significant microvessel complications, of which nephropathy, retinopathy and neuropathy are the most commonly studied. Although clinically evident microvascular complications of diabetes are rarely seen in childhood, early vascular abnormalities develop during childhood and accelerate during puberty.2. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis, which is regulated by endothelial nitric oxide synthase (NOS3) at several levels. Together, VEGF and NOS3 play an important role in the pathogenesis of the microvascular complications of diabetes.3. Genetic variations in NOS3 and VEGF critically regulate endothelial survival and function and increase the susceptibility of patients to develop severe microvessel complications.4. Identification of the risk factors for and improved understanding of the subclinical signs of these diabetic microvascular complications will enable implementation of therapeutic strategies, potentially changing the course of vascular complications and improving the prognosis of children, adolescents and young adults with diabetes.5. Moreover, early detection of these variations may have a prognostic value or may suggest interventional approaches to regulate these proteins in patients with diabetes.

Iron accumulation and lipid peroxidation: implication of ferroptosis in diabetic cardiomyopathy

“…These diabetes-induced microvascular damage reduces the oxygen and other nutrients that are supplied to the heart muscle. These microvascular injuries can further aggravate the impairment of the function of the coronary endothelial cells and the increase in the hardness of the microvascular cells due to persistent diabetes [ 160 – 162 ]. One of the primary target tissues for iron overload injury, which is thought to be caused by an excess of ROS, is vascular endothelial cells (VECs) [ 163 , 164 ].…”

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon

“…The angiogenesis-related tube formation assay was conducted using human coronary artery endothelial cells (HCAECs) to demonstrate the strong angiogenic property of NO released from NO-Lipo containing disulfide bonding group. NO is an endothelial survival factor, inhibiting apoptosis and accelerating proliferation of EC, 40,41 with an increase in the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF) by upregulating the expression of nitric oxide synthase (NOS) in the body. 41,42 Taken together, the exogenous disulfide bonding group is expected to facilitate the continuous NO release reaction with GSH and SNAP in the blood vessel.…”

Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy

“…The pathological mechanisms of DMCM are not fully established, although multiple potential mechanisms have been proposed, including endothelial cell dysfunction, microangiopathy, damage from reactive oxygen species, oxidative stress, and mitochondrial dysfunction [ 7 – 10 ]. Microangiopathy with endothelial cell dysfunction is especially problematic, leading to disruption of coronary vascular autoregulation and subsequent impairment of cardiomyocyte maintenance and survival [ 11 ]. Effective therapies to restore the microcirculation are therefore essential, especially in patients with diabetes.…”

“…Effective therapies to restore the microcirculation are therefore essential, especially in patients with diabetes. Unfortunately, such treatments are lacking, as CABG and PCI may address macrovascular disease but do not ameliorate microvascular disease [ 11 – 13 ].…”