Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:

Saturday, June 10, 2017

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

You need both Angiogenesis and Arteriogenesis. What the fuck is your doctor doing? ANYTHING AT ALL?

Arteriogenesis versus angiogenesis

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

Haibo Wang and M. Elizabeth Hartnett *
The John A. Moran Eye Center, University of Utah, 65 N. Mario Capecchi Drive, Salt Lake City, UT 84132, USA
Correspondence: Tel.: +1-801-213-4044; Fax: +1-801-581-3357
Academic Editor: Masuko Ushio-Fukai
Received: 11 April 2017 / Accepted: 31 May 2017 / Published: 3 June 2017


Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis.
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); NOX2; NOX4; NOX1; NOX5; vascular endothelial cell; angiogenesis; neovascularization; vascular inflammation; oxygen-induced retinopathy; eye; retina

1. Introduction

Angiogenesis is the formation of new blood vessels from pre-existing ones [1] and includes physiologic vascularization [2,3], vascular restoration in response to ischemia and other stresses implicated in cardiovascular diseases [4,5], and pathologic neovascularization [6], such as that seen in tumor growth [7,8,9,10] and ocular diseases [6,11,12,13]. Reactive oxygen species (ROS) act as signaling molecules to promote endothelial cell (EC) proliferation, migration and tube formation, which are essential events in angiogenesis. As a major source of ROS generation in vascular ECs [14], nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is of primary interest in understanding the roles of ROS in these biologic events.
The NOX family has seven isoforms, NOX1-5, Dual oxidase 1 (Duox-1) and Doux-2. Of these seven isoforms, catalytic subunits, Nox1, Nox2, Nox4 and Nox5 are expressed in vascular ECs [14,15]. Enzymatic activation of NOX1-2 requires assembly of the catalytic subunit, Nox1 or Nox2, with regulatory subunits, p22phox (also known as cytochrome b-245 alpha chain), and p47phox or NADPH oxidase organizer 1 (Noxo1), p67phox or NADPH oxidase activator 1 (Noxa1), p40phox and ras-related C3 botulinum toxin substrate 1 (Rac1) [14]. Nox subunits and p22phox are membrane-bound proteins, and p47phox (Noxo1), p67phox (Noxa1), p40phox and Rac1 are cytosolic. However, activation of NOX4 does not require the recruitment of cytosolic subunits and is constitutively active through its interaction with p22phox. NOX5 is activated by Ca2+ and does not require other subunits to be active but may interact with p22phox [4,14]. Activation of NOX is often measured by ROS generation. It is generally accepted that under physiologic conditions, vascular NOX shows relatively low activity as assessed by ROS generation; however, activity can be increased in response to both acute and chronic stimuli, such as growth factors, cytokines, chemokines, hypoxia or ischemia [4].
Over the past decade, the roles of NOX in angiogenesis have been extensively studied. In this review, we provide an update of the new findings of NOX in regulating physiologic and pathologic angiogenesis in ocular vascular diseases, cardiovascular diseases, and tumor angiogenesis, with emphasis on the roles of NOX2 and NOX4, which are best known in vascular diseases. We also discuss molecular mechanisms involved in the activation of NOX and NOX-mediated signaling pathways in angiogenesis and the crosstalk between vascular inflammation and pathologic angiogenesis.


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