Metalloproteinases and their inhibitors in neurological disease

Lopez-Navarro, Edgar R.; Gutierrez, José

doi:10.1007/s00210-021-02188-x

Cited by 13 publications

(9 citation statements)

References 76 publications

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“…Within the CNS, MMPs participate both in (i) physiological processes such as neurogenesis, axonal guidance, synaptic plasticity, learning, and memory [ 69 ] and (ii) in pathological conditions such as neuroinflammation, neurodegeneration, and cerebrovascular related disorders [ 70 ].…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Trentini

Manfrinato

Castellazzi

et al. 2022

JPM

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It is now established that sex differences occur in clinical manifestation, disease progression, and prognosis for both cardiovascular (CVDs) and central nervous system (CNS) disorders. As such, a great deal of effort is now being put into understanding these differences and turning them into “advantages”: (a) for the discovery of new sex-specific biomarkers and (b) through a review of old biomarkers from the perspective of the “newly” discovered sex/gender medicine. This is also true for matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix (ECM) remodelling, which play a role in both CVDs and CNS disorders. However, most of the studies conducted up to now relegated sex to a mere confounding variable used for statistical model correction rather than a determining factor that can influence MMP levels and, in turn, disease prognosis. Consistently, this approach causes a loss of information that might help clinicians in identifying novel patterns and improve the applicability of MMPs in clinical practice by providing sex-specific threshold values. In this scenario, the current review aims to gather the available knowledge on sex-related differences in MMPs levels in CVDs and CNS conditions, hoping to shed light on their use as sex-specific biomarkers of disease prognosis or progression.

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Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Trentini

Manfrinato

Castellazzi

et al. 2022

JPM

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“…22–25 These proteolytic enzymes regulate extracellular proteins in the tunica media and can lead to increased elastin and collagen degradation, resulting in increased arterial diameters. 26 Some MMPs (ie, MMP-9) associated with brain arterial dilation have been proposed to play a role in brain disorders closely related to cerebrovascular morbidities, such as small vessel disease and Alzheimer disease. 27–29 This shared underlying pathophysiology is supported by robust evidence on the relationship between larger brain arterial diameters and imaging signatures of small vessel disease, 5,30–33 as well as worse cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS

Brutto

Khasiyev

Omran

et al. 2023

ATVB

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Background: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. Methods: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. Results: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03–2.23], BA aHR, 1.28 [95% CI, 1.02–1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02–3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07–8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. Conclusions: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

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“…Regarding the IMF phenotype, the term matrix metalloproteinase 2 was identified, referring to a family of endopeptidases that are involved in the remodeling of extracellular matrix components [ 49 ]. Extracellular matrix enzymes are excellent candidates for remodeling body fat [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association (GWAS) Applied to Carcass and Meat Traits of Nellore Cattle

Reis,

Carvalho,

Espigolan

et al. 2023

Metabolites

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The meat market has enormous importance for the world economy, and the quality of the product offered to the consumer is fundamental for the success of the sector. In this study, we analyzed a database which contained information on 2470 animals from a commercial farm in the state of São Paulo, Brazil. Of this total, 2181 animals were genotyped, using 777,962 single-nucleotide polymorphisms (SNPs). After quality control analysis, 468,321 SNPs provided information on the number of genotyped animals. Genome-wide association analyses (GWAS) were performed for the characteristics of the rib eye area (REA), subcutaneous fat thickness (SFT), shear force at 7 days’ ageing (SF7), and intramuscular fat (IMF), with the aid of the single-step genomic best linear unbiased prediction (ssGBLUP) method, with the purpose of identifying possible genomic windows (~1 Mb) responsible for explaining at least 0.5% of the genetic variance of the traits under analysis (≥0.5%). These genomic regions were used in a gene search and enrichment analyses using MeSH terms. The distributed heritability coefficients were 0.14, 0.20, 0.18, and 0.21 for REA, SFT, SF7, and IMF, respectively. The GWAS results indicated significant genomic windows for the traits of interest in a total of 17 chromosomes. Enrichment analyses showed the following significant terms (FDR ≤ 0.05) associated with the characteristics under study: for the REA, heat stress disorders and life cycle stages; for SFT, insulin and nonesterified fatty acids; for SF7, apoptosis and heat shock proteins (HSP27); and for IMF, metalloproteinase 2. In addition, KEGG (Kyoto encyclopedia of genes and genomes) enrichment analysis allowed us to highlight important metabolic pathways related to the studied phenotypes, such as the growth hormone synthesis, insulin-signaling, fatty acid metabolism, and ABC transporter pathways. The results obtained provide a better understanding of the molecular processes involved in the expression of the studied characteristics and may contribute to the design of selection strategies and future studies aimed at improving the productivity of Nellore cattle.

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Metalloproteinases and their inhibitors in neurological disease

Cited by 13 publications

References 76 publications

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases

Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS

Genome-Wide Association (GWAS) Applied to Carcass and Meat Traits of Nellore Cattle

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