Cardiac Ischemia and Ischemia/Reperfusion Cause Wide Proteolysis of the Coronary Endothelial Luminal Membrane: Possible Dysfunctions

Arroyo-Flores, Blanca L.; Chi‐Ahumada, Erika; Briones-Cerecero, Erika; Barajas-Espinosa, Alma; Perez-Aguilar, Sandra; Rosa, Ana Paulina Barba de la; Knabb, Maureen; Rubio, Rafael

doi:10.2174/1874192401105010239

Cited by 4 publications

(2 citation statements)

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“…Receptor-proteins for several hormones are present in the endothelial luminal membrane. Moreover, in the luminal endothelial membrane, the presence of at least fourteen receptor-proteins has been established: Angiotensin AT1 and AT2, insulin, endothelin, prolactin, vasopressin, thromboxane A2, adenosine A1, A2, and A3, bradykinin, adrenergic α, β1, and β3 are present [12]- [14], [17], [43]- [45]. Fig.…”

Section: ) the Endothelial Luminal Membrane Of Many Organs Can Be Reliably Isolatedmentioning

confidence: 99%

“…In summary, the following membrane receptors are present in the endothelial lumen: Angiotensin AT1 and AT2, insulin, endothelin, prolactin, vasopressin, thromboxane A2, and adenosine A1, A2, and A3, bradykinin, adrenergic α, β1, and β3 [12]- [14], [18], [43]- [45]. These and other luminal receptors can be hormone-activated or block.…”

Section: ) Only a Vascular Antagonist Blocks Vascular Agonist Effects While Interstitially The Antagonist Has No Actionmentioning

confidence: 99%

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The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

Rubio

2021

EJMED

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In 1849, the first list of endocrine hormones was discovered and proposed that the synthesizing gland delivers it to the circulation. The circulatory hormone reaches the target organ, physically unimpeded acts directly on the parenchymal cells. Such a simplistic view persists despite new knowledge of an endothelial wall barrier and implications for every parenchymal cell in the body. This misconception leads to inadequate interpretations of data, wrong diagnosis and therapeutic expectations, erroneous hypotheses, and misleads further research work. The quest of this review is to play down this misconception by pointing out key overlooked findings of the vascular endothelial wall: 1) The selective endothelial barrier physically separates two same-hormone-containing compartments; the endocrine and the interstitial autocrine hormone compartments, 2) the hormone concentrations values in these compartments are independent of each other, 3) in each compartment the hormone acts solely on the receptors of that particular compartment, 4) multiple intravascular endocrine hormones act solely on their corresponding luminal endothelial membrane receptor (LEMR), without directly acting on the parenchymal cells, 5) Agonist-activation of LEMR triggers the release of specific paracrine endothelial agents that in conjunction with autocrine interstitial hormone modulate parenchymal function(s) and perhaps the turnover of the interstitial autocrine hormone, 6) these hormone compartments, functionally interact via paracrine exchange signaling, and the integrated intercourse of all these events result in the final hormonal organ effect. The present challenges to achieving more rationale therapeutic effects are to design agonists or antagonists that exclusively gain access to a target compartment and have high specificity for the receptor of the cells in that compartment.

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Section: ) the Endothelial Luminal Membrane Of Many Organs Can Be Reliably Isolatedmentioning

confidence: 99%

Section: ) Only a Vascular Antagonist Blocks Vascular Agonist Effects While Interstitially The Antagonist Has No Actionmentioning

confidence: 99%

The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

Rubio

2021

EJMED

Self Cite

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Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function

et al. 2013

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There is evidence that H2R blockade improves ischemia/reperfusion (I/R) injury, but the underlying cellular mechanisms remain unclear. Histamine is known to increase vascular permeability and induce apoptosis, and these effects are closely associated with endothelial and mitochondrial dysfunction, respectively. Here, we investigated whether activation of the histamine H2 receptor (H2R) exacerbates myocardial I/R injury by increasing mitochondrial and endothelial permeability. Serum histamine levels were measured in patients with coronary heart disease, while the influence of H2R activation was assessed on mitochondrial and endothelial function in cultured cardiomyocytes or vascular endothelial cells, and myocardial I/R injury in mice. The serum histamine level was more than twofold higher in patients with acute myocardial infarction than in patients with angina or healthy controls. In neonatal rat cardiomyocytes, histamine dose-dependently reduced viability and induced apoptosis. Mitochondrial permeability and the levels of p-ERK1/2, Bax, p-DAPK2, and caspase 3 were increased by H2R agonists. In cultured human umbilical vein endothelial cells (HUVECs), H2R activation increased p-ERK1/2 and p-moesin levels and also enhanced permeability of HUVEC monolayer. All of these effects were abolished by the H2R blocker famotidine or the ERK inhibitor U0126. After I/R injury or permanent ischemia, the infarct size was reduced by famotidine and increased by an H2R agonist in wild-type mice. In H2R KO mice, the infarct size was smaller; myocardial p-ERK1/2, p-DAPK2, and mitochondrial Bax were downregulated. These findings indicate that H2R activation exaggerates myocardial I/R injury by promoting myocardial mitochondrial dysfunction and by increasing cardiac vascular endothelial permeability.

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Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine

Černý

Astapenko

Brettner

et al. 2017

Critical Reviews in Clinical Laboratory Sciences

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The purpose of this manuscript is to review the role of endothelial glycocalyx (EG) in the field of critical and perioperative medicine and to discuss possible future directions for investigations in this area. Under physiological conditions, EG has several well-defined functions aimed to prevent the disruption of vessel wall integrity. Under pathological conditions, the EG represent one of the earliest sites of injury during inflammation. EG structure and function distortion contribute to organ dysfunction related to sepsis, trauma, or global ischemia of any origin. Discovering new therapeutic approaches (either pharmacological or non-pharmacological) aimed to protect the EG against injury represents a promising direction in clinical medicine. Further, the currently-used common interventions in the acutely ill - fluids, blood products, nutritional support, organ-supporting techniques (e.g. continuous renal replacement therapy, extracorporeal circulation), temperature modulation and many others - should be re-evaluated during acute illness in terms of their EG "friendliness". To assess new therapies that protect the EG, or to evaluate the effect of currently-used interventions on EG integrity, a relevant marker or method to determine EG damage is needed. Such marker or method should be available to clinicians within hours, preferably in the form of a point-of-care test at the bedside. Collaborative research between clinical disciplines and laboratory medicine is warranted, and targeting the EG represents major challenges for both.

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Cardiac Ischemia and Ischemia/Reperfusion Cause Wide Proteolysis of the Coronary Endothelial Luminal Membrane: Possible Dysfunctions

Cited by 4 publications

References 34 publications

The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function

Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine

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