Gene profiling in isolated microvessels from DM type 1 animals demonstrated deregulated expression of 54 genes related to angiogenesis, inflammation, vasoconstriction/vasodilation, and platelet activation pathways by at least 2-fold (including eNOS, TNFα, TGFβ1, VCAM-1, E-selectin, several chemokines, and MMP9).
This study demonstrates the regulatory mechanism of Sp1-mediated MMP-9 expression in diabetic wound healing and highlights the potential therapeutic benefits of miR-129 and -335 in delayed wound healing in diabetes.
The mechanism associated with diabetes and AF may be attributed to oxidative stress (ROS production) derived from NOX activity, and then induced activation of the MAPK signaling pathways and MMP9 expression.
Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus.
MMP-9 promoter has binding sites for many transcription factors, and in diabetes its promoter undergoes epigenetic modifications, including histone modifications and DNA methylation.
MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (β = -31.3, p = 0.04).
In a streptozotocin-induced diabetes mouse model, Nrf2(-/-) mice have delayed wound closure rates compared with Nrf2(+/+) mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis.
SV exposed to DM conditions demonstrated a notable increase in MMP-2 and MMP-9 but a significant decrease in TIMP-2 and TIMP-3 in protein concentration compared with control group.
To understand how diabetes increases mitochondrial accumulation of MMP-9, interactions between MMP-9 and chaperone proteins (heat shock protein [Hsp] 70 and Hsp60) were evaluated.
Although no significant main effects were observed for MMP-9 -1562 C>T locus on CAD risk, variant genotypes of -1562 C>T were associated with a 2.53 increased risk of CAD in subjects with diabetes mellitus (DM) (95% CI = 1.18-5.45, P = 0.018).
Increased urinary excretion of NGAL and MMP-9 supports a role for NGAL/MMP-9 dysregulation in renal dysfunction; moreover, gender-specific differences could support a gender contribution to pathological mechanisms or susceptibility for the development of renal complications in diabetes mellitus.
Multivariate logistic regression analysis with adjustment for the prevalence of diabetes mellitus revealed that the 1615G-->A polymorphism of BCHE, the 7,067,365C-->A polymorphism of INSR, the C-->T polymorphism of GPX1, the G-->A polymorphism of ROS1, and the G-->A polymorphism of MMP9 were associated (P<0.05) with in-stent restenosis.
Plasma MMP-9 (p=0.027) and TIMP-1 (p=0.016) concentrations were significantly greater, and the ratio of plasma TIMP-1:MMP-9 concentrations significantly lower, in the diabetes group (p=0.023).
The increased MMP-1, MMP-2 and MMP-9 activities induced by high glucose exposure could promote matrix degradation thereby accelerating atherogenesis and potentially reducing plaque stability in diabetes.
These differences may be contributing to the impaired healing of the diabetes mouse; however, they differ from the human data presented here, which show elevated matrix metalloproteinase 2 and reduced matrix metalloproteinase 9 in human diabetic chronic wound fluid compared to acute wound fluid.