Harmandeep Kaur

Max Planck Institute for Heart and Lung Research · Department II Pharmacology

Background Several new treatments have recently been shown to have heart and kidney protective benefits in people with diabetes. Because these treatments were developed in parallel, it is unclear how the different molecular pathways affected by the therapies may overlap. Here, we examined the effects of the mineralocorticoid receptor antagonist fin...

Introduction & Objective: Several new treatments have recently been shown to have kidney protective benefits in people with diabetes. Because these treatments were developed in parallel, at the time of their clinical trial participation many individuals were not receiving concurrent treatment with other therapies subsequently also found to have kid...

Introduction & Objective: Epigenetic processes and inflammation have each emerged as key players in the development of diabetic kidney disease. Here, we compared the consequences of knockout of the epigenetic enzyme and histone demethylase, KDM6B from myeloid cells in diabetic mice and mice with obstructive uropathy. Methods: Myeloid cell KDM6B kno...

Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO). However, tub...

Background and Purpose Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G‐protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. Experimental Approach RNA sequ...

Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (...

Introduction: Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how cardiomyocytes respond to accumulating inflammatory cells within the remodeling heart and how this response, in turn, affects heart function. Methods: Experiments were performed in mouse and rat models of press...

Simple Summary Hypertension or high blood pressure is a long-term incurable clinical condition characterized by persistent high blood pressure in arteries. Constant pressure overload in the heart leads to cardiac remodeling involving hypertrophy, alteration of gene expression, extracellular matrix molecule deposition, and cardiac fibrosis. In the l...

Purpose of review Delayed graft function (DGF) is a significant complication that contributes to poorer graft function and shortened graft survival. In this review, we sought to evaluate the current and emerging role of medical imaging modalities in the assessment of DGF and how it may guide clinical management. Sources of information PubMed, Goog...

Cervical cancer is one of the leading causes of mortality amongst women in developing countries, and resistance to therapy is the main reason for treatment failure. Recent advances suggest that cancer stem cells (CSCs) are critically involved in regulating the chemo-resistant behavior of cervical cancer cells. In our study, cells with the CSC pheno...

In the past few years there has been a rapid expansion of interest in the study of single cells, especially through the new techniques that involve single-cell RNA sequencing (scRNA-seq). Recently, these techniques have provided new insights into kidney health and disease, including insights into diabetic kidney disease (DKD). However, despite the...

The causes of the increased risk of severe COVID-19 in persons with diabetes are unclear. It has been speculated that renin angiotensin system (RAS) blockers may promote COVID-19 by increasing ACE2, which SARS-CoV-2 uses to enter host cells, along with the host protease TMPRSS2. Taking a reverse translational approach and by combining in situ hybri...

Breast cancer is one of the genetic diseases causing a high mortality among women around the world. Despite the availability of advanced diagnostic tools and treatment strategies, the incidence of breast cancer is increasing every year. This is due to the lack of accurate and reliable biomarkers whose deficiency creates difficulty in early breast c...

Background: G-protein-coupled receptors (GPCRs) are important regulators of contractility and differentiation in vascular smooth muscle cells (SMC), but the specific function of SMC-expressed orphan GPCR GPRC5B is unclear. Methods: We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMC in vitr...

The original version of this Article omitted the following from the Acknowledgements: ‘This project was supported by CRC128/Project A03 of the Deutsche Forschungsgemeinschaft (DFG).’This has not been corrected in either the PDF or HTML versions.

GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encep...

G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expressio...

Supplementary Figures and Supplementary Tables.

Blast analysis of sequencing results of single-cell amplificates obtained with forward (F) and reverse (R) primers. The E-value describes the number of hits expected to see by chance when searching a database of a comparable size. An E-value of 1 indicates that in a database of the current size one might expect to see 1 match with a similar score s...

mRNA sequencing results for 80 individual murine aortic smooth muscle cells.

Despite our increasing understanding of zebrafish heart development and regeneration, there is limited information about the distribution of endothelial cells (ECs) in the adult zebrafish heart. Here, we investigate and compare the distribution of cardiac ECs (cECs) in adult mouse and zebrafish ventricles. Surprisingly, we find that (i) active coro...

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing...

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse...

Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial...

Quantification of aISVs and vISVs number.The number of aISVs and vISVs was quantified at 154 hpf in control and Tg(hsp70l:sflt4); Tg(kdrl:EGFP) fish, which were given no heat shock or multiple heat shocks at 29, 36, and 43 hpf. The 10 ISVs directly anterior to the anal opening on both sides of the body (total 20 ISVs) were used for quantification (...

Quantification of average number of somites that showed ectopic blood vessels in flt1+/+ and flt1bns29/+ larvae.Animals were treated with DMSO or 50 µM Mtz between 30 and 154 hpf, and quantification was performed at 154 hpf (10 somites examined per animal; 23–33 animals examined per condition).DOI: http://dx.doi.org/10.7554/eLife.20253.019

Vascular networks surrounding individual organs are important for their development, maintenance, and function; however, how these networks are assembled remains poorly understood. Here we show that CNS progenitors, referred to as radial glia, modulate vascular patterning around the spinal cord by acting as negative regulators. We found that radial...

Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress...

Background and aims: Despite the clinical importance of atherosclerosis, the origin of cells within atherosclerotic plaques is not fully understood. Due to the lack of a definitive lineage-tracing strategy, previous studies have provided controversial results about the origin of cells expressing smooth muscle and macrophage markers in atherosclero...

Rationale: Activated cardiac fibroblasts (CF) are crucial players in the cardiac damage response; excess fibrosis, however, may result in myocardial stiffening and heart failure development. Inhibition of activated CF has been suggested as a therapeutic strategy in cardiac disease, but whether this truly improves cardiac function, is unclear. Obj...

Elevated blood pressure is a key risk factor for developing cardiovascular diseases. Blood pressure is largely determined by vasodilatory mediators, such as nitric oxide (NO), that are released from the endothelium in response to fluid shear stress exerted by the flowing blood. Previous work has identified several mechanotransduction signaling proc...

The inhibitor of the nuclear factor-kappaB (IkappaB) kinase (IKK) complex is a key regulator of the canonical NF-kappaB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-kappaB activation; however, there is increasing evidence for N...

Scavenger receptors (SR) are the cell surface proteins that can bind and internalize modified lipoproteins. Because ox-LDL seems to play a key role in foam cell formation during atherogenesis, SR may be critical for pathogenesis of atherosclerosis. The present study was aimed to study the effect of selenium (Se) supplementation on SR, i.e., SRB1 an...

Atherosclerosis is a chronic disorder of the arterial wall that starts by formation of fatty streaks and gradually evolves into atherosclerotic plaques. High-density lipoproteins (HDL) blood levels are inversely correlated with atherosclerosis. This beneficial effect of HDL has been partly attributed to its antioxidant properties mediated by paraox...