-
Revista Portuguesa de Cardiologia :... Nov 2023Peripartum cardiomyopathy is a rare type of heart failure manifesting towards the end of pregnancy or in the months following delivery, in the absence of any other cause... (Review)
Review
Peripartum cardiomyopathy is a rare type of heart failure manifesting towards the end of pregnancy or in the months following delivery, in the absence of any other cause of heart failure. There is a wide range of incidence across countries reflecting different population demographics, uncertainty over definitions and under-reporting. Race, ethnicity, multiparity and advanced maternal age are considered important risk factors for the disease. Its etiopathogenesis is incompletely understood and is likely multifactorial, including hemodynamic stresses of pregnancy, vasculo-hormonal factors, inflammation, immunology and genetics. Affected women present with heart failure secondary to reduced left ventricular systolic function (LVEF <45%) and often with associated phenotypes such as LV dilatation, biatrial dilatation, reduced systolic function, impaired diastolic function, and increased pulmonary pressure. Electrocardiography, echocardiography, magnetic resonance imaging, endomyocardial biopsy, and certain blood biomarkers aid in diagnosis and management. Treatment for peripartum cardiomyopathy depends on the stage of pregnancy or postpartum, disease severity and whether the woman is breastfeeding. It includes standard pharmacological therapies for heart failure, within the safety restrictions for pregnancy and lactation. Targeted therapies such as bromocriptine have shown promise in early, small studies, with large definitive trials currently underway. Failure of medical interventions may require mechanical support and transplantation in severe cases. Peripartum cardiomyopathy carries a high mortality rate of up to 10% and a high risk of relapse in subsequent pregnancies, but over half of women present normalization of LV function within a year of diagnosis.
Topics: Pregnancy; Female; Humans; Peripartum Period; Cardiomyopathies; Heart Failure; Prognosis; Echocardiography; Puerperal Disorders; Pregnancy Complications, Cardiovascular
PubMed: 37414337
DOI: 10.1016/j.repc.2023.01.029 -
Translational Oncology Aug 2023Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to...
Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to overcome chemoresistance and improve clinical outcomes in patients who have failed chemotherapy. Using a two-tier phenotypic screening platform, we identified bromocriptine mesylate as a potent and selective inhibitor of chemoresistant PCa cells. Bromocriptine effectively induced cell cycle arrest and activated apoptosis in chemoresistant PCa cells but not in chemoresponsive PCa cells. RNA-seq analyses revealed that bromocriptine affected a subset of genes implicated in the regulation of the cell cycle, DNA repair, and cell death. Interestingly, approximately one-third (50/157) of the differentially expressed genes affected by bromocriptine overlapped with known p53-p21- retinoblastoma protein (RB) target genes. At the protein level, bromocriptine increased the expression of dopamine D2 receptor (DRD2) and affected several classical and non-classical dopamine receptor signal pathways in chemoresistant PCa cells, including adenosine monophosphate-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa B (NF-κB), enhancer of zeste homolog 2 (EZH2), and survivin. As a monotherapy, bromocriptine treatment at 15 mg/kg, three times per week, via the intraperitoneal route significantly inhibited the skeletal growth of chemoresistant C4-2B-TaxR xenografts in athymic nude mice. In summary, these results provided the first preclinical evidence that bromocriptine is a selective and effective inhibitor of chemoresistant PCa. Due to its favorable clinical safety profiles, bromocriptine could be rapidly tested in PCa patients and repurposed as a novel subtype-specific treatment to overcome chemoresistance.
PubMed: 37271121
DOI: 10.1016/j.tranon.2023.101707 -
Annals of Medicine and Surgery (2012) Feb 2024Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also... (Review)
Review
Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also serving as a selective agonist on D2 dopamine receptors as a dopamine receptor agonist. Apart from prolactin inhibiting action, bromocriptine has some beneficial effects on the blood pressure, plasma norepinephrine levels and vascular resistance. Dopamine D2 receptor activation of bromocriptine is associated with the antihypertensive effect, which lowers blood pressure via inhibiting sympathetic nerve activity and Na/K ATPase activity. Plasma levels of the pro-inflammatory cytokines such as interleukin (IL)-1B and IL-18, chemokine CCL2/ MCP-1/, and the pro-inflammatory hormone prolactin, all of which are elevated and linked to accelerated cardiometabolic illness, were decreased because of bromocriptine therapy. The most common side effects of Bromocriptine use are dizziness, nausea, headache, vomiting and hypotension. Bromocriptine is mainly contraindicated in patients with syncope with hypotension, psychosis, and type I diabetes mellitus. The authors suggest that developing therapies directed to increase D2 receptor expression and function by drugs like Bromocriptine can provide practical and novelistic approaches to prevent and manage myocardial and renal injury in the cardiovascular disease patients.
PubMed: 38333315
DOI: 10.1097/MS9.0000000000001642