Stimulator of interferon genes associated vasculopathy with onset in infancy (SAVI), caused by heterozygote gain-of-function mutations in TMEM173, is characterized by fever attacks with ulcerating cutaneous manifestations on cold-sensitive areas and interstitial lung disease.
Furthermore, an inverse correlation of intravesicular miR-92a in blood serum and KLF4 expression in lesions was observed in atherosclerotic animals, indicating the potential function of extracellular miR-92a in regulating vascular diseases.
This selective microvascular effect may connote a therapeutic potential for MPO inhibition in the prevention of vascular disease/dysfunction seen in IR humans.
In the present article, we summarize recent findings, review the molecular mechanisms and the potential of SIRT1 as a therapeutic target for the treatment of vascular diseases, and discuss future research directions.
By contrast, late-onset sporadic AD (LO-SAD) is a multifactorial disorder in which age-related changes, genetic risk factors, such as allelic variation in apolipoprotein E (Apo E) and many other genes, vascular disease, TBI and risk factors associated with diet, the immune system, mitochondrial function, metal exposure, and infection are all implicated.
In fact, emerging data have provided fundamental rationale for Klotho-based therapeutic intervention for vascular diseases and multiple other potential indications.
Our study identifies WNT5A and its downstream vascular signaling as a link between obesity and vascular disease pathogenesis, with translational implications in humans.
MiR-21, miR- 31, and miR-155 are of particular interest owing to their important involvement in both SSc vasculopathy and fibroproliferative alterations.
Our data suggest that suppression of TFEB may be an initiating mechanism that promotes SMC dedifferentiation leading to accelerated neointima formation in vascular disorders associated with metabolic stress, whereas trehalose reverses these changes.
The use of transgenic and gene knockout animals, gene manipulated cells, pharmacological LPA receptor agonists and antagonists have provided many insights into the biological significance of LPA and individual LPA receptors in the progression of atherosclerosis and vascular diseases.
Our findings demonstrate a key role for Nur77 in the maintenance of lung endothelial barrier protection to LPS and suggest that therapeutic strategies aimed at augmenting Nur77 levels might be effective in treating a wide variety of inflammatory vascular diseases of the lung.