Significance of plasma relaxin-2 levels in patients with primary hypertension and type 2 diabetes mellitus.

BACKGROUND: This study aimed to evaluate plasma relaxin­2 (RLN-2) levels in patients with arterial hypertension (AH) and their relationships with clinical and laboratory parameters. METHODS: The study involved 106 hypertensive patients, including 55 with type 2 diabetes mellitus (T2DM), and 30 control subjects. Plasma RLN-2 levels were measured using an enzyme-linked immunosorbent assay kit. RESULTS: RLN-2 levels were reduced in patients with AH compared to healthy volunteers (p < 0.001), and hypertensive patients with T2DM had lower RLN-2 levels than those without impaired glucose metabolism (p < 0.001). RLN­2 was negatively correlated with systolic blood pressure (SBP) (p < 0.001) and anthropometric parameters such as body mass index (BMI; p = 0.027), neck (p = 0.045) and waist (p = 0.003) circumferences, and waist-to-hip ratio (p = 0.011). RLN­2 also had inverse associations with uric acid levels (p = 0.019) and lipid profile parameters, particularly triglycerides (p < 0.001) and non-HDL-C/HDL­C (p < 0.001), and a positive relationship with HDL­C (p < 0.001). RLN­2 was negatively associated with glucose (p < 0.001), insulin (p = 0.043), HbA1c (p < 0.001), and HOMA-IR index (p < 0.001). Univariate binary logistic regression identified RLN­2 as a significant predictor of impaired glucose metabolism (p < 0.001). CONCLUSIONS: Decreased RLN-2 levels in patients with AH and T2DM and established relationships of RLN­2 with SBP and parameters of glucose metabolism and lipid profile suggest a diagnostic role of RLN­2 as a biomarker for AH with T2DM.

Relaxin-2 plasma levels in atrial fibrillation are linked to inflammation and oxidative stress markers.

Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H2O2 plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-ß1 (TGF-ß1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Relationships between reproductive hormones and maternal pregnancy physiology in women conceiving with or without in vitro fertilization.

We evaluated maternal pregnancy adaptations and their relationships with circulating hormones in women who conceived with or without in vitro fertilization (IVF). Pregnancies were grouped by corpus luteum (CL) number: 1 CL with physiological plasma relaxin concentration (PRLN; spontaneous pregnancies); 0 CL without circulating RLN (programmed cycles); >1 CL with elevated PRLN (ovarian stimulation). Major findings were that declines in plasma osmolality (Posm) and plasma sodium concentration ([Formula: see text]) were comparable in the 1 CL and 0 CL cohorts, correlated with plasma estradiol and progesterone concentrations but not PRLN; gestational declines in plasma uric acid (UA) concentration (PUA) were attenuated after IVF, especially programmed cycles, partly because of subdued increases of renal UA clearance; and PRLN and cardiac output (CO) were inversely correlated when plasma estradiol concentration was below ∼2.5 ng/mL but positively correlated above ∼2.5 ng/mL. Unexpectedly, PRLN and plasma sFLT1 (PsFLT1) were directly correlated. Although PsFLT1 and CO were not significantly associated, CO was positively correlated with plasma placental growth factor (PLGF) concentration after the first trimester, particularly in women who conceived with 0 CL. Major conclusions are that 1) circulating RLN was unnecessary for gestational falls in Posm and [Formula: see text]; 2) PRLN and CO were inversely correlated during early gestation, suggesting that PRLN in the lower range may have contributed to systemic vasodilation, whereas at higher PRLN RLN influence became self-limiting; 3) evidence for cooperativity between RLN and estradiol on gestational changes in CO was observed; and 4) after the first trimester in women who conceived without a CL, plasma PLGF concentration was associated with recovery of CO, which was impaired during the first trimester in this cohort.

Endurance exercise improves avoidance learning and spatial memory, through changes in genes of GABA and relaxin-3, in rats.

Different exercise patterns, neurotransmitters, and some genes have numerous effects on learning and memory. This research aims to investigate the long-term effects of submaximal aerobic exercise on spatial memory (SM), passive avoidance learning (PAL), levels of serum relaxin-3, gamma-aminobutyric acid (GABA), RLN3 gene, and glutamic acid decarboxylase (GAD65/67 genes) in the brainstem of adult male Wistar rats. Fifty male Wistar rats were randomly divided into five groups: aerobic exercise groups, performed on a treadmill running (TR), for 5 weeks (Ex5, n = 10), 10 weeks (Ex10, n = 10), involuntary running wheel group for 5 weeks (IRW5, n = 10), sham (Sh, n = 10) and control (Co, n = 10). Consequently, SM, PAL, serum relaxin-3, GABA, and GAD65/67 and RLN3 genes were measured by ELISA and PCR. Ex5, Ex10 and IRW5 improved significantly SM (p ≤ 0.05), PAL (p ≤ 0.001) and decreased significantly relaxin-3 (p ≤ 0.001). RLN3 in the brain also decreased. However, it was not significant. GABA and GAD65/GAD67 increased significantly (p ≤ 0.05) in Ex5, Ex10 compared to Sh and Co. Aerobic exercise enhanced SM and PAL in Ex compared to Co and Sh. However, duration and type of exercise affected the level of enhancement. The serum relaxin-3 and RLN3 gene displayed reverse functions compared to GABA and GAD65/67 genes in Ex. Therefore, the changes of neurotransmitters in serum relaxin-3, GABA, and their genes: RLN3 and GAD65/67 respectively, influenced learning and memory meaningfully.

H3 relaxin protects against calcium oxalate crystal-induced renal inflammatory pyroptosis.

OBJECTIVES: Calcium oxalate (CaOx) crystals can activate inflammatory cytokines by triggering inflammasomes, which cause damage to the adhered epithelium, a dysfunctional microenvironment and even renal failure. However, a comprehensive and in-depth understanding of the mechanisms underlying the effects of these crystals on damage and cytokine function in renal tubular epithelial cells (TECs) remains limited and to be explored. MATERIALS AND METHODS: We detected the pyroptosis of TECs induced after exposure to CaOx crystals and demonstrated the significance of cytokine activation in the subsequent inflammatory processes through a proteomic study. We then conducted animal and cell experiments to verify relevant mechanisms through morphological, protein, histological and biochemical approaches. Human serum samples were further tested to help explain the pathophysiological mechanism of H3 relaxin. RESULTS: We verified that crystal-induced extracellular adenosine triphosphate (ATP) upregulation via the membrane purinergic 2X7 receptor (P2X7 R) promotes ROS generation and thereby activates NLRP3 inflammasome-mediated interleukin-1ß/18 maturation and gasdermin D cleavage. Human recombinant relaxin-3 (H3 relaxin) can act on the transmembrane receptor RXFP1 to produce cAMP and subsequently improves crystal-derived damage via ATP consumption. Additionally, endogenous relaxin-3 was found to be elevated in patients with renal calculus and can thus serve as a biomarker. CONCLUSIONS: Our results provide previously unidentified mechanistic insights into CaOx crystal-induced inflammatory pyroptotic damage and H3 relaxin-mediated anti-inflammatory protection and thus suggest a series of potential therapeutic targets and methods for but not limited to nephrocalcinosis.

Circulating pregnancy hormone relaxin as a first trimester biomarker for preeclampsia.

OBJECTIVE: Preeclampsia, a multi-system hypertensive disorder, is associated with perturbations in the maternal cardiovascular system during early pregnancy. The corpus luteal hormone relaxin, a potent vasodilator, may contribute to physiological circulatory changes especially in early gestation when circulating levels are highest. This study investigated whether first trimester circulating relaxin may be a suitable biomarker for the early prediction of preeclampsia. METHODS: Relaxin was initially measured in first-trimester samples of women who developed late-onset preeclamptic (LO-PE; delivery ≥ 34 weeks; n = 33) and uncomplicated pregnancies (n = 25) in Pittsburgh, USA. Subsequently, to expand the group numbers, relaxin was measured in women who developed LO-PE (n = 95), early-onset preeclamptic (EO-PE; delivery < 34 weeks; n = 57), and uncomplicated pregnancies (n = 469) in Utrecht, the Netherlands. RESULTS: In the Pittsburgh subjects, low relaxin levels (lowest centile:

The Relationship between Serum Relaxin Concentrations and Knee Valgus.

Female athletes are at an elevated risk for tearing their anterior cruciate ligament, compared to their male counterparts. Though injury screening clinical tests and neuromuscular training programs have been widely implemented, injury rates remain high among female athletes. The purpose of this study was to examine the relationship between serum relaxin concentrations and knee valgus during three clinical tests (single leg squat, drop vertical jump, and single leg crossover dropdown). Twenty-two female athletes volunteered. Participants were scheduled for collection during the mid-luteal phase, when serum relaxin concentrations are known to be measurable. Blood samples were collected, and serum relaxin concentrations were quantified. Kinematic data were collected while participants performed the three clinical tests. Regression analyses revealed statistically significant relationships between serum relaxin concentrations and knee valgus throughout all tests. These findings suggest that serum relaxin concentrations and knee valgus are not independent of each other and more holistic approaches may be necessary to truly map out the risk for injury and ultimately reduce the rate of anterior cruciate ligament injuries. Thus, concluding that knee valgus, a highly utilized modifiable biomechanical risk factor, and relaxin, a hormone that has been associated with anterior cruciate ligament injury in female athletes, are related to each other.

Administration study of recombinant human relaxin-2 in horse for doping control purpose.

The insulin-like peptide relaxin (RLX), an endogenous peptide hormone produced in human for pregnancy and reproduction, is also known to exert a range of physiological and pathological effects. Its use is banned in human sports, horseracing, and equestrian competitions due to its potential performance enhancing effect through vasodilation resulting in the increase of blood and oxygen supplies to muscles. Little is known about the biotransformation and elimination of RLX in horses. This paper describes an administration study of rhRLX-2 and its elimination in horses, and the development of sensitive methods for the detection and confirmation of rhRLX-2 in both horse plasma and urine by nano-liquid chromatography/high resolution mass spectrometry (nano-LC/HRMS) after immunoaffinity extraction with the objective of controlling the abuse of rhRLX-2 in horses. The limits of detection in plasma and urine are 2 pg/mL and 5 pg/mL, respectively. Two thoroughbred geldings were each administered one dose of 10 mg rhRLX-2 subcutaneously daily for 3 consecutive days. The rhRLX-2 could be detected and confirmed in the plasma and urine samples collected 105 h and 80 h, respectively, after the last dose of administration. For doping control purposes, rhRLX-2 ELISA could be used as a screening test to identify potential positive samples for further investigation using the nano-LC/HRMS methods.

Serum relaxin level predicts recurrence of atrial fibrillation after radiofrequency catheter ablation.

Relaxin, an emerging biomarker in heart failure, is involved in fibrosis and inflammation. The value of relaxin in predicting recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) is unknown and the subject of this study. We prospectively enrolled 248 consecutive patients with AF (paroxysmal in 127 and persistent in 121) who underwent RFCA at our center after measurement of circulating levels of relaxin by ELISA. Kaplan-Meier analysis with log-rank test and multivariate analysis were used to assess the association between pre-RFCA relaxin levels and post-RFCA AF recurrence at 18 months follow-up. At mean 16.3 ± 3.8 months post-RFCA, 195 (78.6%) patients maintained sinus rhythm, and their pre-RFCA relaxin level was lower than that in patients with AF recurrence (P < 0.001). From lowest to highest pre-RFCA relaxin level tertiles (T1; 82.10-< 234.36; T2; 234.36-< 342.26; and T3; 342.26-740.63 ng/L), AF recurrence rate increased significantly (8.5%, 20.5% and 34.9%, respectively; Kaplan-Meier analysis with log-rank test, χ2 = 18.44, P < 0.001). Using a cutoff of 285.4 ng/L, pre-RFCA relaxin level predicted AF recurrence during follow-up with sensitivity of 77.4% and specificity of 55.9% (area under the receiver operating characteristic curve = 0.71). On multivariate Cox proportional hazard model, relaxin level by tertile (T2, hazard ratio 2.678; 95% confidence interval 1.110-6.460; P = 0.028, and T3, hazard ratio 4.745; 95% confidence interval 2.075-10.854; P < 0.001, respectively compared with the T1) was the independent factor predicting recurrence. Elevated pre-RFCA relaxin level is associated with post-RFCA AF recurrence. A simple measurement of relaxin level therefore might help identify patients at high risk of AF recurrence after RFCA.Clinical Trial Registration chictr.org.cn identifier: ChiCTR-OOC-15006130.

Effect of Mode of Conception on Maternal Serum Relaxin, Creatinine, and Sodium Concentrations in an Infertile Population.

OBJECTIVE: To investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations. BACKGROUND: Pregnancies achieved by fertility treatment often begin in a nonphysiologic endocrine milieu with no corpus luteum (CL) or with many corpora lutea. The CL produces not only estradiol and progesterone but is also the sole source of relaxin in early pregnancy, a hormone that may contribute to maternal systemic and renal vasodilation. There is limited data about maternal physiology in early pregnancy during fertility treatment, and studies have rarely considered the potential effect of the absence of the CL. To begin to address this gap in knowledge, we sought to investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations. METHODS: One hundred eighty-four women who received care at an academic infertility practice provided serum samples. Levels of relaxin 2, creatinine, and electrolytes were compared between 4 groups defined on the basis of mode of conception which corresponded to categories of CL number: (1) absence of the CL, (2) single CL, (3) multiple CL from ovarian stimulation not including in vitro fertilization (IVF), and (4) multiple CL from IVF with fresh embryo transfer. RESULTS: Relaxin-2 levels were undetectable in patients lacking a CL. Creatinine, sodium, and total CO2 levels were significantly higher in the 0 CL group (relaxin absent) compared to all other groups (relaxin present). Compared to clomiphene, use of letrozole was associated with a lower relaxin level. CONCLUSION: Early creatinine and sodium concentrations are increased in the absence of relaxin. Given the increasing utilization of frozen embryo transfer, further studies comparing programmed with natural cycles are warranted.

Is maternal serum relaxin associated with preterm delivery in Chinese pregnant women? A meta-analysis.

Objective: A meta-analysis was performed to study the relationship between serum relaxin and preterm delivery in women with singleton pregnancies without estrogen stimulation. Methods: Cohort and case-control studies were identified through searching databases (PubMed, Embase, Ovid, CBM, Wan fang, VIP, and CNKI). We carried out a continuous variable meta-analysis. The outcome was preterm delivery (gestation age <37 weeks). Results: Fifteen studies were included, involving 1607 women with a singleton pregnancy. The pooled standard mean deviation (SMD) of 15 studies was 0.559 (95%CI: 0.002-1.196) and the heterogeneity was 96.6%. To reduce the heterogeneity, we chose random effects model and made subgroup analysis according to gestational age at sample testing (<18 weeks and ≥18 weeks) and race of included pregnant women. The pooled SMD of gestational age at sample testing ≥18 weeks and Chinese were 1.19 (95%CI: 0.63-1.75) and 1.61 (95%CI: 0.82-2.41) and the heterogeneity values (measured by I2) were 93.5% and 76.5%, respectively. Conclusions: Elevated maternal serum relaxin of later than 18 weeks of gestational age is associated with singleton preterm birth in Chinese women. It might be an important information to prevent singleton preterm delivery in Chinese women. What's already known about this topic? Previous reports reveal that there is a relationship between elevated maternal serum relaxin and preterm birth. However, the included articles contained twin pregnancies and estrogen stimulation, which obviously resulted in higher relaxin concentrations. What does this study add?

The impact of apelin and relaxin plasma levels in masked hypertension and white coat hypertension.

Masked hypertension (HTN) and white coat hypertension represent two reverse forms of clinical HTN with questionable prognostic significance. Recent evidence supports that low apelin and relaxin plasma levels contribute to vascular damage accelerating atherogenesis and predisposing to HTN and cardiovascular (CV) events. The aim of this study was to compare apelin and relaxin plasma levels between patients with masked hypertension (MH) and those with white coat HTN (WCH). Overall, 130 patients not receiving antihypertensive therapy were studied. All patients underwent 24-hour ambulatory BP monitoring (ABPM) and office BP measurements. Plasma apelin and relaxin levels were measured by ELISA method. According to BP recordings, 24 subjects had MH (group A) and 32 had WCH (group B). Apelin (200 ± 111 pg/mL vs 305 ± 127 pg/mL, P < 0.01) and relaxin (35.2 ± 6.7 pg/mL vs 46.8 ± 23.6 pg/mL, P < 0.01) plasma levels were significantly lower in patients with MH compared to those with WCH, respectively. In conclusion, our findings showed that patients with MH had significantly lower apelin and relaxin levels compared to those with WCH. This observation implies an additional prognostic role for adipokines supporting the concept that MH is closer to essential HTN whereas WCH is a more benign condition.

Cardiac magnetic resonance using late gadolinium enhancement and atrial T1 mapping predicts poor outcome in patients with atrial fibrillation after catheter ablation therapy.

To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation times were assessed using CMR. Plasma levels of relaxin, myeloperoxidase and serum levels of matrix metalloproteinase (MMP)-mediated cardiac specific titin fragmentation and MMP-mediated type IV collagen degradation were obtained. Poor outcome was defined by the recurrence of AF during 1-year follow-up. 61 patients were included in final analysis. Twenty (32.8%) patients had recurrence of AF. Patients with a recurrence of AF had a higher percentage of LA LGE (26.7 ± 12.5% vs. 17.0 ± 7.7%; P < 0.001), higher LA T1 relaxation times (856.7 ± 112.2 ms vs. 746.8 ± 91.0 ms; P < 0.001) and higher plasma levels of relaxin (0.69 ± 1.34 pg/ml vs. 0.37 ± 0.88 pg/ml; P = 0.035). In the multivariate Cox regression analysis, poor ablation outcome was best predicted by advanced LGE stage (hazard ratio (HR):5.487; P = 0.001) and T1 relaxation times (HR:1.007; P = 0.001). Pre-procedural CMR is a valuable tool for prediction of poor response to catheter ablation therapy in patients with AF. It offers various imaging techniques for outcome prediction and might be valuable for a better patient selection prior to ablation therapy.

Longitudinal profiles of relaxin and progestagens during pregnancy, pregnancy loss and false pregnancy in the killer whale (Orcinus orca).

The circulating pattern of immunoreactive relaxin and progestagens based on monthly and gestational stage (early, mid, late) profiles were determined during pregnancies that resulted in live calves (LIVE, n = 30), stillbirths (STILLB, n = 3), abortions (ABORT, n = 5) and presumptive false pregnancies (FALSE, n = 8), and during the follicular (n = 34) and luteal phase (n = 58). Monthly LIVE relaxin concentrations steadily increased during gestation, but values did not significantly exceed those of the luteal phase until 9 months prior to parturition, peaking during the final month at 2356 ng/ml. Relaxin surged (P < 0.05) during the final week of gestation (36,397 ng/ml), undergoing a 3 and 9-fold increase compared with concentrations in the preceding two weeks, respectively. Monthly relaxin production did not differ among each reproductive state with the exception of months-13-16 where concentrations were higher (P < 0.001) for STILLB than LIVE. Relaxin concentration was reduced (P < 0.0001) by 849% in placental versus maternal serum collected within 1 day of labor. Mid- and late-pregnancy progestagen concentrations were lower for FALSE (P < 0.001) compared with STILLB and LIVE. Late pregnancy progestagen concentrations were reduced for FALSE (P < 0.05) and ABORT (P < 0.02) compared with LIVE and STILLB. Monthly progestagen production in ABORT tended to be lower than LIVE across a range of gestational months (Months 2, 7, 8, 11) but this difference only became significant during months 14 and 15. Results indicate that relaxin is primarily produced by the CL during pregnancy, and that concentrations could not be used to differentiate from non-pregnant females until the final 6 months of gestation. In addition, as would be expected from a primarily CL product, relaxin cannot be used to detect abnormal pregnancies. Conversely, progestagens, which are produced by both the placenta and CL can be used to differentiate FALSE from normal pregnancy and may be useful indicators of fetal health in the killer whale.

The subset of patients with acute heart failure able to secrete relaxin-2 at pregnancy concentrations could have a longer survival: a pilot study.

OBJECTIVE: To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome. METHODS: In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 < 500 pg/mL). The primary outcome was all-cause death during follow-up. Secondary endpoints were prolonged hospitalisation (>10 days), combined endpoint (death, rehospitalisation, ED revisit) 30 days after discharge, and 30-day, one-year and three-year death rates. RESULTS: We included 814 patients [81 (SD = 9) years; 53.0% women] followed during 1.9 (SD 2.8) years; 517 (63.5%) died. Twenty patients (2.5%) formed the PLG (median relaxin-2 = 1459 pg/mL; IQR = 1722) and 794 the CG (median = 26; IQR = 44). There was no interaction with variables included on adjustment (age, sex, ischaemic cardiomyopathy, NT-proBNP, glycaemia, and sodium). PLG patients did not have better short-term secondary endpoints, but did show a significantly lower three-year mortality [ORadjusted = 0.17 (0.05-0.5), p = 0.003]. CONCLUSIONS: The small proportion of AHF patients achieving relaxin-2 concentrations similar to those observed in pregnancy may survive longer.

Associations between serum relaxin 2, aneurysm formation/size and severity of atherosclerosis: a preliminary prospective analysis.

Serum relaxin 2 (RL2) is a pleiotropic hormone that acts on various organs and systems, particularly the cardiovascular system. Although RL2 seems to upregulate the synthesis of nitric monoxide (NO) and matrix metalloproteinase (MMP)-2 and -9, current literature on its role in atherosclerosis and aneurysm formation is scarce. The aim of this study was to investigate the levels of serum RL2 in patients with an arterial aneurysm as well as in atherosclerotic patients, and correlate them with the severity of their related vascular disease. A total of 53 subjects were enrolled in this study: 37 patients were scheduled to undergo surgery: 21 patients for different forms of atherosclerotic disease (ATH), 16 patients for an arterial aneurysm (AA), 6 patients for undergoing temporal artery biopsy (TAB), and 10 healthy blood donors (HBD) served as the control groups. RL2 was measured using enzymelinked immunosorbent assay. RL2 was significantly higher in AA patients compared to ATH (P<0.01), TAB (P<0.001) and HBD (P<0.01). No significant difference was found between the ATH and TAB groups (P>0.05). In addition, ATH and AA patients were further subdivided based on the severity of their disease. Serum RL2 was progressively increased in patients with arterial aneurysms, showing a positive relationship with the size of the aneurysmatic dilatation. By contrast, the RL2 level was inversely related to the severity of the atherosclerotic disease. Studies with a larger cohort incorporating a consistent study population are warranted to verify our results and shed light on the mechanistic background of these processes.

Decreased Serum Relaxin-2 Is Correlated with Impaired Islet ß-Cell Function in Patients with Unstable Angina and Abnormal Glucose Metabolism.

Circulating relaxin (RLX) is altered in patients with diabetes mellitus (DM) or cardiovascular diseases. This study was designed to evaluate the changes of RLX in patients with unstable angina (UA) complicated with various categories of abnormal glucose metabolism.Patients who confirmed UA by angiographic and clinical standard were grouped according to the glucose metabolism status with oral glucose tolerance test (OGTT) and medical history categorized as normal, prediabetes, newly diagnosed type 2 DM (T2DM), and previously diagnosed T2DM. Serum RLX-2 was measured and islet ß-cell function was evaluated. The severity of the coronary arterial lesions was evaluated with Syntax Scores.Serum RLX-2 was significantly higher in UA patients with prediabetes (median [quartiles]: 9.87 [7.48, 32.58] pg/mL) and newly diagnosed T2DM (18.36 [9.52, 48.08] pg/mL), compared with those with normal glucose tolerance (6.24 [4.02, 7.27] pg/mL, both P < 0.05). Interestingly, UA patients with previously diagnosed T2DM exhibited lower RLX-2 levels (4.17 [3.23, 5.72] pg/mL) compared with those with normal glucose tolerance (P < 0.05). Subsequent analyses indicated that serum RLX-2 was positively associated with parameters of islet ß-cell function, C-peptide, and fasting insulin levels; however, it was negatively associated with the levels of fasting glucose, 2-hour postprandial blood glucose, HbA1c, and insulin sensitivity, suggesting a potential protective role of RLX-2 during abnormal glucose metabolism in UA patients. Serum RLX-2 was not correlated with the Syntax Scores in these patients.Serum RLX-2 is a potential marker for UA patients with early glucose metabolism abnormality, and increased RLX-2 level was correlated with preserved islet ß-cell function.

Luteal and hypophyseal expression of the canine relaxin (RLN) system during pregnancy: Implications for luteotropic function.

By acting through its receptors (RXFP1, RXFP2), relaxin (RLN) exerts species-specific effects during pregnancy; possible luteotropic effects through stimulation of prolactin (PRL) release have been suggested. In the domestic dog (Canis lupus familiaris) serum PRL increases in pregnant bitches shortly after RLN appears in the circulation, and a possible functional relationship between the RLN and the PRL systems in regulating progesterone secretion has been implied. Therefore, here (Study 1) the luteal expression and localization of the RLN system was investigated by immunohistochemistry using custom-made antibodies and semi-quantitative PCR, at selected time points during gestation: pre-implantation (d. 8-12), post-implantation (d. 18-25), mid-gestation (d. 35-40) and at normal and antigestagen-induced luteolysis. Further, (Study 2) hypophyseal expression of the RLN system and its spatial association with PRL was assessed. Luteal expression of RLN, but not of its receptors, was time-dependent: it increased significantly following implantation towards mid-gestation and decreased at prepartum. Antigestagen treatment resulted in downregulation of RLN and RXFP2. Whereas RLN was localized in steroidogenic cells, RXFP1 and RXFP2 also stained strongly in macrophages and vascular endothelial cells. The RLN system was detected in the canine adenohypophysis and was co-localized with PRL in hypophyseal lactotrophs. The intraluteal RLN seems to be involved in regulating the canine corpus luteum (CL) in a time-dependent manner. The presence of RLN family members in the adenohypophysis implies their possible involvement in regulating the availability of PRL and other pituitary hormones.