Biology subjects

Hinkel, R.

Publications and source records attributed to Hinkel, R..

3 recordsLinked to original sources

bioRxiv2026

Natural aging drives a subclinical cardiovascular phenotype in a non-human primate

Aging is an inevitable risk factor for cardiovascular disease. Profound understanding of mechanisms underlying the early stages of cardiovascular aging is essential for the development of novel therapeutics. Therefore, animal models which closely reflect the human condition are highly sought after. Here, we investigated natural cardiovascular aging in a non-human primate, comparing healthy young-adult and aged common marmosets (Callithrix jacchus). Despite preservation of most cardiac functional parameters in aged animals, significant histological alterations were found including fibrosis and microvascular rarefaction. Molecular phenotyping by single-nuclei RNA-sequencing revealed activation of cardiac stress, pro-inflammatory and fibrotic gene programs in aged hearts. Importantly, proteomic analysis of cardiac extracellular vesicles revealed a cardioprotective cargo in young animals while functionally demonstrating pro-angiogenic properties on human cardiac microvascular endothelial cells. Finally, large vessel atherosclerosis was strikingly evident in aged animals and elucidated by bulk RNA-sequencing. Overall, the aging marmoset offers a great potential for translational cardiovascular research.

physiology↗

bioRxiv2024

Single neuron diversity supports area functional specialization along the visual cortical pathways

Humans and other primates have specialized visual pathways composed of interconnected cortical areas. The input area V1 contains neurons that encode basic visual features, whereas downstream in the lateral prefrontal cortex (LPFC) neurons acquire tuning for novel complex feature associations. It has been assumed that each cortical area is composed of repeatable neuronal subtypes, and variations in synaptic strength and connectivity patterns underlie functional specialization. Here we test the hypothesis that diversity in the intrinsic make-up of single neurons contributes to area specialization along the visual pathways. We measured morphological and electrophysiological properties of single neurons in areas V1 and LPFC of marmosets. Excitatory neurons in LPFC were larger, less excitable, and fired broader spikes than V1 neurons. Some inhibitory fast spiking interneurons in the LPFC had longer axons and fired spikes with longer latencies and a more depolarized action potential trough than in V1. Intrinsic bursting was found in subpopulations of both excitatory and inhibitory LPFC but not V1 neurons. The latter may favour temporal summation of spikes and therefore enhanced synaptic plasticity in LPFC relative to V1. Our results show that specialization within the primate visual system permeates the most basic processing level, the single neuron.

neuroscience↗

bioRxiv2019

Agrin promotes coordinated therapeutic processes leading to improved cardiac repair in pigs

Ischemic heart diseases are classified among the leading cause of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a significant number of MI patients develop chronic heart failure over time. We have recently reported that a fragment of the extra cellular matrix (ECM) protein Agrin promotes cardiac regeneration following MI in adult mice. Here, we tested the therapeutic potential of Agrin in a preclinical porcine model, comprising either 3 or 28 days (d) reperfusion period. We first demonstrate that local (antegrade) delivery of recombinant human Agrin (rhAgrin) to the infarcted pig heart can target the affected regions in an efficient and clinically-relevant manner. Single dose of rhAgrin resulted in significant improvement in heart function, infarct size, fibrosis and adverse remodeling parameters 28 days post MI. Short-term MI experiment along with complementary murine MI studies revealed myocardial protection, improved angiogenesis, inflammatory suppression and cell cycle re-entry, as Agrins mechanisms of action. We conclude that a single dose of Agrin is capable of reducing ischemia reperfusion injury and improving cardiac function, demonstrating that Agrin could serve as a therapy for patients with acute MI and potentially heart failure.

physiology↗