Objective Transient, repetitive occlusion stimulates collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early in CCG then return to contractile phenotype. CCG is impaired in the metabolic syndrome. We determined whether impaired CCG was due to aberrant VSMC phenotypic modulation by miR-145-mediated mechanisms and if restoration of physiological miR-145 levels in metabolic syndrome (JCR rat) improved CCG. Approach/Results CCG was stimulated by transient, repetitive LAD occlusion and evaluated after 9 days by coronary blood flow measurements (microspheres). miR-145 was delivered to JCR VSMCs via adenoviral vector (miR-145-Adv). In JCR rats, miR-145 was decreased late in CCG (~2 fold day 6; ~4 fold day 9 vs. SD), which correlated with decreased expression of SM-specific contractile proteins (~5 fold day 6; ~10 fold day 9 vs. SD) indicative of VSMCs’ failure to return to the contractile phenotype late in CCG. miR-145 expression in JCR rats (miR-145-Adv) on days 6–9 of CCG completely restored VSMCs contractile phenotype and CCG (CZ/NZ flow ratio was 0.93±0.09 JCR+miR-145-Adv vs. 0.12±0.02 JCR vs. 0.87±0.02 SD). Conclusions Restoration of VSMC contractile phenotype through miR-145 delivery is a highly promising intervention for restoration of CCG in the metabolic syndrome.

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There have been several studies regarding the use of laser therapy for the treatment of GSM. Most of these studies show a trend toward safe and effective treatment in the short term (less than or equal to 12 weeks). However, these studies are lacking in randomization, blinding, placebo, and comparison groups. Although laser therapy for the treatment of the symptoms of GSM appears promising, there is currently a lack of high-level and long-term evidence regarding its safety and efficacy. There is also a lack of professional guidelines in the USA regarding this modality of treatment, specifically for GSM. Opportunities exist for future research in this area, specifically to determine safety and long-term outcomes of therapy.

. Antiapoptotic Bcl-2, phospho-Bad, and Bcl-2/Bax dimers were increased on days 6 and 9 RI, and proapoptotic Bax and Bax/Bax dimers and cytochrome-c release concurrently decreased in JCR versus SD rats. Active caspases were decreased in JCR versus SD rats (ϳ50%). Neutrophils increased transiently on day 3 RI in the collateraldependent zone of SD rats but remained elevated in JCR rats, paralleling miR-21 expression. miR-21 downregulation by antimiR-21 induced neutrophil apoptosis and decreased Bcl-2 and Bcl-2/

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Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura (P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.