Exercise training causes a partial improvement through increasing testosterone and eNOS for erectile function in middle-aged rats.

Purpose: Aging changes the balance of sex hormones and causes endothelial dysfunction in the penis, both of which are important determinants of erectile dysfunction (ED). The purpose of this study was to evaluate whether exercise training could protect against erectile dysfunction by increasing serum testosterone and penile eNOS levels in aging rats.

Methods: A total of 14 young (2-month-old) and 14 middle-aged (18-month-old) Sprague Dawley rats were randomly assigned to either untrained control (young control, [YC], middle-aged control, [MC]) or endurance exercise-trained (young exercise, [YE], middle-aged exercise, [ME]) groups with seven rats per group.

Glucocorticoid receptor positively regulates transcription of FNDC5 in the liver.

Irisin is secreted by skeletal muscle during exercise and influences energy and metabolic homeostasis. This hormone is a cleaved and secreted fragment of fibronectin type III domain-containing 5 (FNDC5). Elucidation of the FNDC5 gene regulation mechanism is necessary to clarify the function of irisin as a potential therapeutic target in human metabolic diseases.

Mechanical stretch enhances the expression and activity of osteopontin and MMP-2 via the Akt1/AP-1 pathways in VSMC.

Hemodynamic forces causing mechanical stretch (MS) of vascular smooth muscle cells (VSMC) play an important role in vascular remodeling, but the underlying mechanism involved is not fully understood. Thus, this study investigated whether osteopontin (OPN) expression in VSMC was induced by MS, and identified the intracellular signaling pathways involved in OPN production. The plasma level of OPN and its expression in aortic tissue were increased in various animal models of hypertension including spontaneous hypertensive rats and hypertensive mice induced by angiotensin II or L-NAME.

LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways.

5-Lipoxygenase (5-LO) plays a pivotal role in the progression of atherosclerosis. Therefore, this study investigated the molecular mechanisms involved in 5-LO expression on monocytes induced by LPS. Stimulation of THP-1 monocytes with LPS (0~3 µg/ml) increased 5-LO promoter activity and 5-LO protein expression in a concentration-dependent manner.

TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells.

Resistin derived from diabetic perivascular adipose tissue up-regulates vascular expression of osteopontin via the AP-1 signalling pathway.

Perivascular adipose tissue (PVAT) is implicated in the development of vascular diseases; however, the roles of PVAT on OPN expression in diabetic vasculature remain to be determined. This study investigated the role of adipokines derived from diabetic PVAT in regulating the vascular expression of OPN and explored the mechanisms involved. Aortic sections of ob/ob and high-fat diet (HFD)-induced obese (DIO) mice showed an increased expression of OPN, which was paralleled by increased amounts of PVAT characterized by enlargement of adipocytes.

Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.

Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS). When VSMC was stimulated with MS (0-10% strain, 60 cycles/min), both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner.

5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes via an increased expression of Mac-1.

Aims: 5-Lipoxygenase (5-LO) is known to participate in the pathogenesis of atherosclerosis; however, the underlying mechanisms are unclear. Thus, this study investigated the molecular mechanisms responsible for 5-LO expression in monocytes as well as the role of 5-LO in monocyte adhesion to the vascular endothelium, which is a key early event in macrophage foam cell formation.

Methods And Results: An en face immunohistochemistry of endothelial surfaces revealed a marked increase in monocyte adhesion to the aortic endothelium in wild-type (WT) mice treated with lipopolysaccharide (LPS), which was significantly attenuated in 5-LO((-/-)) mice.

Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase.

Gomisin J (GJ) is a lignan contained in Schisandra chinensis (SC) which is a well-known medicinal herb for improvement of cardiovascular symptoms in Korean. Thus, the present study examined the vascular effects of GJ, and also determined the mechanisms involved. Exposure of rat thoracic aorta to GJ (1-30μg/ml) resulted in a concentration-dependent vasorelaxation, which was more prominent in the endothelium (ED)-intact aorta.

Antihypertensive effect of gomisin A from Schisandra chinensis on angiotensin II-induced hypertension via preservation of nitric oxide bioavailability.

Gomisin A (GA) is a small molecular weight lignan present in Schisandra chinensis, and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of GA on blood pressure (BP) in angiotensin II (Ang II)-induced hypertensive mice. C57/BL6 mice infused subcutaneously with Ang II (1 and 2 μg kg⁻¹ per min for 2 weeks) showed an increase in BP with a decrease in nitric oxide (NO) metabolites in plasma, and a negative correlation between these two parameters was demonstrated.

Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways.

Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.

Cilostazol Attenuates 4-hydroxynonenal-enhanced CD36 Expression on Murine Macrophages via Inhibition of NADPH Oxidase-derived Reactive Oxygen Species Production.

Although anti-atherogenic effects of cilostazol have been suggested, its effects on the expression of SR in macrophages are unclear. This study investigated the role of cilostazol on CD36 expression of murine macrophages enhanced by HNE, a byproduct of lipid peroxidation. The stimulation of macrophages with HNE led to an increased expression of CD36, which was significantly attenuated by NAC, an antioxidant.

Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta.

Schisandra chinensis (SC), a member of the Magnoliaceae family, has been used to improve the vascular health for postmenopausal women in Korea. In order to provide some scientific rationales for such effectiveness, this study investigated the vascular effects of gomisin A (GA) from SC. In the endothelium (ED)-intact rings of rat thoracic aorta, GA (1 x 10 (-6) to 3 x 10 (-4) M) caused a concentration-dependent relaxation which was markedly attenuated not only by removal of ED but also by pretreatment with N(G)-nitro- L-arginine (10 (-4) M) or 1 H-[1,2,4]oxadiazol[4,3- a]quinoxalin-1-one (3 x 10 (-5) M).