The Pathologic Continuum of Diabetic Vascular Disease

Abstract

Hyperglycemia can promote vascular complications by multiple mechanisms, with formation of advanced glycation endproducts (AGEs) and increased oxidative stress proposed to contribute to both macrovascular and microvascular complications. Many of the earliest pathologic responses to hyperglycemia are manifest in the vascular cells that directly encounter elevated blood glucose levels. In the macrovasculature, these include endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). In the microvasculature, these include ECs, pericytes (in retinopathy), and podocytes (in renal disease). Additionally, neovascularization arising from the vasa vasorum may promote atherosclerotic plaque progression and contribute to plaque rupture, thereby interconnecting macro- and microangiopathy.

Decelerated vascularization in tissue-engineered constructs in association with diabetes mellitus in vivo

“…The increased expression of endothelial adhesion molecules is triggered by the excessive production of advanced glycation end products (AGEs) during hyperglycemia [47]. Additionally, AGEs themselves cause an elevated oxidative stress level in endothelial cells [48,49]. In addition, an ischemia study in diabetic rats showed higher numbers of rolling leukocytes in the mesenteric venules [50].…”

“…Considerably increased differentiation of MSCs to adipocytes may be another reason for the reduced angiogenic capacity [37]. Concerning diabetic microangiopathy the thickening of the basement membrane has to be considered [49].…”

Do We Need A Wider Therapeutic Paradigm For Heart Failure With Comorbidities?: A Remote Australian Perspective

“…Increasing blood levels directly contributes to and progresses CHF. AGE can secondarily lead to CHF by a vast array of negative effects on healthy organs [21][22][23][24][25][26][27][28][29][30][31][32]. In summary there are common overlaps in activating regulatory systems and consequences of homeostatic imbalances.…”

“…Difficulties for the NT include bd dosing, hypotensive effects, achieving top dose and reduced quality of life data in some studies. Metoprolol XR, bisoprolol have neutral or negative effects on metabolic profiles, renal blood flow and nocturnal melatonin levels [29]. Of interest is Nebivolol, highly selective with vasodilatory properties through NO potentiation.…”

“…By decreasing peripheral resistance and increasing stroke volume, this effect also increases cardiac output and exercise capacity compared to traditional ββ that blunts CO. Positive effects are seen in renal function/serum K+, erectile function, COAD and pulmonary pressures with an evolving understanding on sleep and cognitive function [13,29,47,48]. There has been some debate over the extent of clinical benefit as NO donor and strength of evidence in severe HF, but is an agent that deserves strong consideration.…”