ArticleHypertension (Dallas, Tex. : 1979)2008
Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat.
Article in Hypertension (Dallas, Tex. : 1979), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01375491 (Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor), which is not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- New insights on the cardiovascular effects of IGF-1.Frontiers in endocrinology · 2023Pooled it
- Aging by autodigestion.PloS one · 2024Article
- A novel modified-curcumin 2.24 resolves inflammation by promoting M2 macrophage polarization.Scientific reports · 2023Article
- Anti-Obesity Effect of Rice Bran Extract on High-Fat Diet-Induced Obese Mice.Preventive nutrition and food science · 2022Article
- Molecular Interactions of Arterial Hypertension in Its Target Organs.International journal of molecular sciences · 2021Review
- Pancreatic Microcirculation Profiles in the Progression of Hypertension in Spontaneously Hypertensive Rats.American journal of hypertension · 2021Article
- Comparison of pancreatic microcirculation profiles in spontaneously hypertensive rats and Wistar-kyoto rats by laser doppler and wavelet transform analysis.Physiological research · 2020Article
- Serum Metabonomic Research of the Anti-Hypertensive Effects of Ogaja on Spontaneously Hypertensive Rats.Metabolites · 2020Article
- Neutrophil Modulation in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Leukocyte matrix metalloproteinase and tissue inhibitor gene expression patterns in children with primary hypertension.Journal of human hypertension · 2020Article
- Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis.Reproductive biology and endocrinology : RB&E · 2020Article
- Pancreatic source of protease activity in the spontaneously hypertensive rat and its reduction during temporary food restriction.Microcirculation (New York, N.Y. : 1994) · 2019Article
- Cleavage of the leptin receptor by matrix metalloproteinase-2 promotes leptin resistance and obesity in mice.Science translational medicine · 2018Article
- IGF-1 receptor cleavage in hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2018Article
- Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction.Advances in pharmacology (San Diego, Calif.) · 2018Review
- Enteral tranexamic acid attenuates vasopressor resistance and changes in α1-adrenergic receptor expression in hemorrhagic shock.The journal of trauma and acute care surgery · 2017Article
- Regulation and involvement of matrix metalloproteinases in vascular diseases.Frontiers in bioscience (Landmark edition) · 2016Review
- The autodigestion hypothesis: Proteolytic receptor cleavage in rheological and cardiovascular cell dysfunction1.Biorheology · 2016Article
- Emergence of a metalloproteinase / phospholipase A2 axis of systemic inflammation.Metalloproteinases in medicine · 2015Article
- Proteolytic receptor cleavage in the pathogenesis of blood rheology and co-morbidities in metabolic syndrome. Early forms of autodigestion.Biorheology · 2015Review
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2 authors at 1 institution in 1 country.
Funding
Abstract
Arterial hypertension is associated with organ dysfunctions, but the mechanisms are uncertain. We hypothesized that enhanced proteolytic activity in the microcirculation of spontaneously hypertensive rats (SHRs) may be a pathophysiological mechanism causing cell membrane receptor cleavage and examine this for 2 different receptors. Immunohistochemistry of matrix-degrading metalloproteinases (matrix metalloproteinase [MMP]-9) protein shows enhanced levels in SHR microvessels, mast cells, and leukocytes compared with normotensive Wistar-Kyoto rats. In vivo microzymography shows cleavage by MMP-1 and -9 in SHRs that colocalizes with MMP-9 and is blocked by metal chelation. SHR plasma also has enhanced protease activity. We demonstrate with an antibody against the extracellular domain that the insulin receptor-alpha density is reduced in SHRs, in line with elevated blood glucose levels and glycohemoglobin. There is also cleavage of the binding domain of the leukocyte integrin receptor CD18 in line with previously reported reduced leukocyte adhesion. Blockade of MMPs with a broad-acting inhibitor (doxycycline, 5.4 mg/kg per day) reduces protease activity in plasma and microvessels; blocks the proteolytic cleavage of the insulin receptor, the reduced glucose transport; normalizes blood glucose levels and glycohemoglobin levels; and reduces blood pressure and enhanced microvascular oxidative stress of SHRs. The results suggest that elevated MMP activity leads to proteolytic cleavage of membrane receptors in the SHR, eg, cleavage of the insulin receptor-binding domain associated with insulin resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.