Hypertension
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Comparative Study
The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-α1C.
Chronic hypoxia is the most common cause of secondary pulmonary hypertension, for which the mechanisms are still unclear. Recent studies implicated an important role for microRNAs (miRNAs) in hypoxia-mediated responses in various cellular processes, including cell apoptosis and proliferation. Therefore, we hypothesized that these regulatory molecules might be implicated in the etiology of hypoxic pulmonary hypertension. ⋯ Furthermore, miRNA-328 suppressed the insulin growth factor 1 receptor, ultimately leading to apoptosis of pulmonary arterial smooth muscle cells. The posttranscriptional repression of L-type calcium channel-α1C and insulin growth factor 1 receptor was further confirmed by luciferase reporter assay. These results showed that miRNA-328, an important protecting factor, plays a significant role in PA constriction and remodeling by regulating multiple gene targets in hypoxic pulmonary hypertension.
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We reported previously that an angiotensin II type 1 receptor blocker, telmisartan, improved cognitive decline with peroxisome proliferator-activated receptor-γ activation; however, the detailed mechanisms are unclear. Enhanced blood-brain barrier (BBB) permeability with alteration of tight junctions is suggested to be related to diabetes mellitus. Therefore, we examined the possibility that telmisartan could attenuate BBB impairment with peroxisome proliferator-activated receptor-γ activation to improve diabetes mellitus-induced cognitive decline. ⋯ These effects of telmisartan were weakened by cotreatment with GW9662. In contrast, administration of another angiotensin II type 1 receptor blocker, losartan, was less effective compared with telmisartan in terms of preventing BBB permeability and astroglial end-foot swelling, and coadministration of GW9662 did not affect the effects of losartan. These findings are consistent with the possibility that, in type 2 diabetic mice, angiotensin II type 1 receptor blockade with peroxisome proliferator-activated receptor-γ activation by telmisartan may help with protection against cognitive decline by preserving the integrity of the BBB.