Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 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:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. 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 lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Sunday, January 19, 2025

Vascular Pharmacology of Epoxyeicosatrienoic Acids

 This phrase means our stroke leadership should get research going to see how this would help stroke recovery. But with NO stroke leadership, NOTHING EVER GETS DONE! YOURE SCREWED AS ARE ALL FOLLOWING STROKE SUVIVORS!

EETs regulate blood vessel formation or angiogenesis

Vascular Pharmacology of Epoxyeicosatrienoic Acids

  • PMCID: PMC3373307  NIHMSID: NIHMS382978  PMID: 21081214

    Abstract

    Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in responses to various stimuli such as the agonists acetylcholine (ACH) or bradykinin or by shear stress which activates phospholipase A2 to release arachidonic acid. EETs are important regulators of vascular tone and homeostasis. In the modulation of vascular tone, EETs function as endothelium-derived hyperpolarizing factors (EDHFs). In models of vascular inflammation, EETs attenuate inflammatory signaling pathways in both the endothelium and vascular smooth muscle. Likewise, EETs regulate blood vessel formation or angiogenesis by mechanisms that are still not completely understood. Soluble epoxide hydrolase (sEH) converts EETs to dihydroxyeicosatrienoic acids (DHETs) and this metabolism limits many of the biological actions of EETs. The recent development of inhibitors of sEH provides an emerging target for pharmacological manipulation of EETs. Additionally, EETs may initiate their biologic effects by interacting with a cell surface protein that is a G-protein coupled receptor (GPCR). Since GPCRs represent a common target of most drugs, further characterization of the EET receptor and synthesis of specific EET agonists and antagonist can be used to exploit many of the beneficial effects of EETs in vascular diseases, such as hypertension and atherosclerosis. This review will focus on the current understanding of the contribution of EETs to the regulation of vascular tone, inflammation and angiogenesis. Furthermore, the therapeutic potential of targeting the EET pathway in vascular disease will be highlighted.

    Keywords: epoxyeicosatrienoic acid, cytochrome P450, endothelial cell, hyperpolarization, angiogenesis, inflammation

    1. Introduction

    Epoxyeicosatrienoic acids (EETs) play a pivotal role in numerous cellular processes involved in vascular function, including vasodilation and inflammation. The multifunctional nature of EETs underlies the importance of these compounds in cardiovascular disease. This review will focus on the current understanding of the contribution of EETs to the regulation of vascular tone, inflammation and angiogenesis. Furthermore, the therapeutic potential of targeting the EET pathway in vascular disease will be highlighted.

    2. Biochemistry

    In endothelial cells, arachidonic acid is metabolized by the cyclooxygenase (COX), lipoxygenase and cytochrome P450 (CYP) epoxygenase pathways (, ). The epoxygenase pathway leads to the formation of four regioisomeric EETs, 14,15-EET, 11,12-EET, 8,9-EET and 5,6-EET (Figure 1) (; ). The EETs are released by endothelial cells in response to receptor agonists such as ACH or bradykinin to function as autocrine and paracrine hormones (; ; ; ; ). The relative abundance of each EET regioisomer differs among vascular beds depending on which CYP isoforms are expressed, as each CYP isoform generates its own unique profile of EET regioisomers. While many CYP isozymes have been identified in blood vessels, endothelial CYP2C8/2C9 and CYP2J2 function in humans to produce mainly 14,15-EET, with lesser amounts of 11,12-EET (; ; ). No EET production is detected in smooth muscle ().

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