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Sensation of incomplete bladder emptying (SIBE) has been shown to be correlated with an elevated post-void residual (PVR) in men, however, the significance of this symptom and whether it correlates with an elevated PVR in women is less clear. In this study, we assessed if SIBE in women is correlated with an elevated PVR and determined the relationship of SIBE to other lower urinary tract symptoms.Women ages ≥18 with lower urinary tract symptoms were eligible. SIBE was defined by a response "sometimes", "most of the time", or "all of the time" to the question "How often do you feel that your bladder has not emptied properly after you have urinated?" on the International Consultation on Incontinence Questionnaire. Frequency and bother of other lower urinary tract symptoms were also assessed to compare their relationship to SIBE. Elevated PVR was defined as ≥100 ml via ultrasound.We prospectively evaluated 95 women, 59% of whom reported SIBE. Compared to women without SIBE, women with SIBE reported more urinary hesitancy (51% vs. 18%, p = 0.002), intermittency (56% vs. 16%, p 0.001), weak stream (36% vs. 5%, p 0.001), dysuria (29% vs. 5%, p = 0.004), and straining (25% vs 5%, p = 0.013). However, there was no difference in elevated PVRs between women with and without SIBE [5/56, 9% vs. 4/39, 10%, (p = 0.99)]. All women, regardless of SIBE, reported higher bother from storage and incontinence symptoms versus voiding symptoms with no difference in overall bother scores.SIBE is a common complaint in women with lower urinary tract symptoms. While women with SIBE reported more voiding symptoms, they were more bothered by storage symptoms. Importantly, most of these women emptied their bladder well and were not more likely to have an elevated PVR than women without SIBE.

Cellular metabolism is increasingly recognized to control immune cell fate and functions. MicroRNA-33 (miR-33) is a central regulator of cellular lipid metabolism that represses genes involved in cholesterol efflux and HDL biogenesis (Abca1, Abcg1) and fatty acid oxidation (Cpt1a, Crot, Ampk). Here we show that by altering the balance of aerobic glycolysis and mitochondrial oxidative phosphorylation, miR-33 inhibition instructs macrophage polarization to an M2 phenotype and shapes innate and adaptive immune responses. Targeted deletion of miR-33 in macrophages increases oxidative phosphorylation, enhances spare respiratory capacity, and induces the expression of genes that define M2 macrophage polarization (Arg1, Fizz1, Cd206, Ym1). Furthermore, inhibition of miR-33 in Abca1-/- macrophages showed that these changes are independent of effects on cholesterol efflux, but instead require miR-33 targeting of the energy sensor AMP-activated protein kinase (AMPK). Notably, inhibition of miR-33 markedly increased macrophage expression of the retinoic acid-producing enzyme Aldh1a2 and retinal dehydrogenase activity both in vitro and in vivo. Consistent with the ability of retinoic acid to foster inducible regulatory T cells, these macrophages had an enhanced capacity to induce FoxP3 expression in naïve CD4+ T cells. Finally, treatment of western diet-fed Ldlr-/- mice with miR-33 inhibitors for 8 weeks (conditions that do not alter HDL cholesterol levels) reduced atherosclerosis progression by 40%, and promoted the accumulation of M2 macrophages and FoxP3+ T regulatory cells in plaques. Collectively, these results identify a novel role for miR-33 in the regulation of macrophage inflammation and show that antagonism of miR-33 is atheroprotective, in part, by reducing plaque inflammation by promoting M2 macrophage polarization and regulatory T cell induction.