Relaxin/serelaxin for cardiac dysfunction and heart failure in hypertension

Chunduri, Prasad; Patel, Shrey A; Levick, Scott P.

doi:10.1016/bs.apha.2022.04.002

Cited by 2 publications

(6 citation statements)

References 108 publications

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“…The ‘human relaxin protein’ has previously been detected by ELISA in the serum of healthy individuals and patients with prostate cancer and heart failure. − Here, we detected by ELISA the relatively high levels of REL1 (as high as ∼7,000 pg/mL) and REL2 (as high as ∼300 pg/mL) in several serum samples of healthy individuals (Figure A, C). IA-SRM measurements confirmed only REL2 in seminal plasma (Figure D).…”

Section: Resultssupporting

confidence: 56%

“…REL2 played a crucial role in preparing the birth canal for parturition , and was elevated in the first trimester , reaching its peak concentrations of 2.2 ng/mL. , Similar to alpha-fetoprotein, levels of REL2 in the subsequent second trimester decreased to 1–1.3 ng/mL. ,, Low levels of REL2 during pregnancy have been associated with recurrent miscarriage, toxemia of pregnancy, spontaneous abortion, ectopic pregnancy, and premature labor. − Those observations suggested that serum REL2 levels could serve as a potential marker of pregnancy complications, such as preeclampsia . In addition, REL2 has been suggested as a marker of ovarian cancer and a therapeutic target of ovarian cancer, fibrosis, and cardiovascular diseases. ,, Patients with serous adenocarcinoma had a median level of 78.1 pg/mL, a concentration well above the LOD of our IA-SRM assay (9.4 pg/mL).…”

Section: Discussionmentioning

confidence: 99%

“…As a result of low abundance in human tissues and proximal fluids, as well as potential immunoassay cross-reactivity, the protein products of the two distinct human genes RLN1 and RLN2 were often called a 'human relaxin protein'. 25,33,34 Previous studies investigated 'relaxin protein' and identified its role as a female and male reproductive hormone, a neuropeptide within the central nervous system, a vasodilator and cardiac stimulant in the cardiovascular system, and an antifibrotic agent. 33,35,36 Expression of the RLN1 gene was observed by RT-PCR in human prostate tissues and the LNCaP prostate cancer cell line.…”

Section: ■ Discussionmentioning

confidence: 99%

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Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Rais,

Drabovich

2024

J. Proteome Res.

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The human relaxins belong to the Insulin/IGF/Relaxin superfamily of peptide hormones, and their physiological function is primarily associated with reproduction. In this study, we focused on a prostate tissue-specific relaxin RLN1 (REL1_HUMAN protein) and a broader tissue specificity RLN2 (REL2_HUMAN protein). Due to their structural similarity, REL1 and REL2 proteins were collectively named a ‘human relaxin protein’ in previous studies and were exclusively measured by immunoassays. We hypothesized that the highly selective and sensitive immunoaffinity-selected reaction monitoring (IA-SRM) assays would reveal the identity and abundance of the endogenous REL1 and REL2 in biological samples and facilitate the evaluation of these proteins for diagnostic applications. High levels of RLN1 and RLN2 transcripts were found in prostate and breast cancer cell lines by RT-PCR. However, no endogenous prorelaxin-1 or mature REL1 were detected by IA-SRM in cell lines, seminal plasma, or blood serum. The IA-SRM assay of REL2 demonstrated its undetectable levels (<9.4 pg/mL) in healthy control female and male sera and relatively high levels of REL2 in maternal sera across different gestational weeks (median 331 pg/mL; N = 120). IA-SRM assays uncovered potential cross-reactivity and nonspecific binding for relaxin immunoassays. The developed IA-SRM assays will facilitate the investigation of the physiological and pathological roles of REL1 and REL2 proteins.

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Section: Resultssupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

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Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Rais,

Drabovich

2024

J. Proteome Res.

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“…Relaxin has previously been suggested as a potential marker of ovarian cancer 43 and therapeutic target of ovarian cancer 95,96 and cardiovascular diseases 24,34,97 . Patients with serous adenocarcinoma exhibited a mean relaxin level of 78.1 pg/mL 43 , and such levels could be verified with our IA-SRM assay.…”

Section: Discussionmentioning

confidence: 99%

“…The "human relaxin protein" has previously been detected by ELISA in serum of healthy individuals and patients with prostate cancer and heart failure [24][25][26][27][28][29] . Here, we detected by ELISA the relatively high levels of REL1 (as high as ~7,000 pg/ml) and REL2 (as high as ~300 pg/ml) in several serum samples of healthy individuals (Figure 5A,C).…”

Section: Measurement Of Rel1 and Rel2 In Blood Serummentioning

confidence: 99%

Identification and quantification of human relaxin proteins by immunoaffinity-mass spectrometry

Rais,

Drabovich

2024

Preprint

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The human relaxins belong to the Insulin/IGF/Relaxin superfamily of peptide hormones, and their physiological function is primarily associated with reproduction. In this study, we focused on a prostate tissue-specific relaxin RLN1 (REL1_HUMAN protein), and a broader tissue specificity RLN2 (REL2_HUMAN). Due to their structural similarity, REL1 and REL2 proteins were collectively named a "human relaxin protein" in previous studies and were exclusively measured by immunoassays. We hypothesized that the highly selective and sensitive immunoaffinity-selected reaction monitoring (IA-SRM) assays could reveal the identity and concentration of REL1 and REL2 in biological samples and facilitate the evaluation of these proteins for diagnostic applications. RT-PCR revealed the high levels of RLN1 and RLN2 transcripts in prostate and breast cancer cell lines. However, no endogenous prorelaxin-1 or mature REL1 were detected by IA-SRM in numerous biological samples. IA-SRM assay of REL2 revealed its undetectable levels (<9 pg/mL) in control female and male sera, relatively high levels of REL2 in maternal sera (median 331 pg/mL, 120 patients), and a biphasic expression of REL2 across the gestational weeks. IA-SRM assays discovered potential cross-reactivity and false-positive measurements for relaxin immunoassays. The developed IA-SRM assays will facilitate the investigation of the physiological and pathological roles of REL1 and REL2 peptide hormones.

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Relaxin/serelaxin for cardiac dysfunction and heart failure in hypertension

Cited by 2 publications

References 108 publications

Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Identification and Quantification of Human Relaxin Proteins by Immunoaffinity-Mass Spectrometry

Identification and quantification of human relaxin proteins by immunoaffinity-mass spectrometry

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