Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1

Omega-3-PUFA, omega-6-PUFA and mitochondrial dysfunction in relation to remodelling

Metabolic syndrome may be a disease of the brain related to Western diet-induced proinflammatory damage of the arcuate nucleus and POMC neurons in the brain, as well as to damage of beta cells in the pancreas. Consumption of a Western diet and eating late at night can double the adverse effects of diet by causing systemic inflammation and damage to the circadian clock machinery, leading to circadian disruption, resulting in metabolic syndrome due to low melatonin and leptin and high cortisol and ghrelin. These neurotransmitters are known to increase oxidative stress, which may damage certain areas of the brain, endothelial cells, and myocardial cells via subcellular remodeling. Increases in free radicals may damage other neurons, macrophages, hepatocytes in the liver, β-cells in the pancreas, and endothelial cells and smooth muscle cells, due to the release of proinflammatory cytokines. Pro-inflammatory cytokines, in conjunction with an underlying deficiency of long-chain PUFA, CoQ10, and polyphenolics, and excess of omega-6-fatty acids, may damage cells in various organs, including pancreatic β-cells, resulting in a further increase in insulin resistance, metabolic syndrome, and diabetes mellitus. © 2018 Nova Science Publishers, Inc. All rights reserved

Omega-3-PUFA, omega-6-PUFA and mitochondrial dysfunction in relation to remodelling

Metabolic syndrome may be a disease of the brain related to Western diet-induced proinflammatory damage of the arcuate nucleus and POMC neurons in the brain, as well as to damage of beta cells in the pancreas. Consumption of a Western diet and eating late at night can double the adverse effects of diet by causing systemic inflammation and damage to the circadian clock machinery, leading to circadian disruption, resulting in metabolic syndrome due to low melatonin and leptin and high cortisol and ghrelin. These neurotransmitters are known to increase oxidative stress, which may damage certain areas of the brain, endothelial cells, and myocardial cells via subcellular remodeling. Increases in free radicals may damage other neurons, macrophages, hepatocytes in the liver, β-cells in the pancreas, and endothelial cells and smooth muscle cells, due to the release of proinflammatory cytokines. Pro-inflammatory cytokines, in conjunction with an underlying deficiency of long-chain PUFA, CoQ10, and polyphenolics, and excess of omega-6-fatty acids, may damage cells in various organs, including pancreatic β-cells, resulting in a further increase in insulin resistance, metabolic syndrome, and diabetes mellitus. © 2018 Nova Science Publishers, Inc. All rights reserved