Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes

Abstract

Cardiorenal syndromes (CRS) include a scenario of clinical interactions characterized by the heart and kidney dysfunction. The crosstalk between cardiac and renal systems is clearly evidenced but not completely understood. Multi-factorial mechanisms leading to CRS do not involve only hemodynamic parameters. In fact, in recent works on organ crosstalk endothelial injury, the alteration of normal immunologic balance, cell death, inflammatory cascades, cell adhesion molecules, cytokine and chemokine overexpression, neutrophil migration, leukocyte trafficking, caspase-mediated induction of apoptotic mechanisms and oxidative stress has been demonstrated to induce distant organ dysfunction. Furthermore, new alternative mechanisms using the multi-omics approach may be implicated in the pathogenesis of cardiorenal crosstalk. The study of “omics” modifications in the setting of cardiovascular and renal disease represents an emerging area of research. Over the last years, indeed, many studies have elucidated the exact mechanisms involved in gene expression and regulation, cellular communication and organ crosstalk. In this review, we analyze epigenetics, gene expression, small non-coding RNAs, extracellular vesicles, proteomics, and metabolomics in the setting of CRS.

Metabolomic profiling of stool of two‐year old children from the INSIGHT study reveals links between butyrate and child weight outcomes

“…This will allow us to leverage “multi‐omics” approaches to consolidate and expand our findings on childhood obesity. “Multi‐omics” approaches are indeed becoming increasingly popular to gain a comprehensive understanding of diseases—including obesity and other metabolic disorders 13,89–93 …”

“…omics" approaches are indeed becoming increasingly popular to gain a comprehensive understanding of diseases-including obesity and other metabolic disorders. 13,[89][90][91][92][93]…”

Progress and Challenges of Understanding Cardiorenal Syndrome Type 3

“…An exponential number of papers have reported direct and indirect mechanisms responsible for cardiac outcomes after AKI since the five CRS classifications creation in 2008; however, the complete mechanisms related to CRS 3 development and a deep understanding of the pathological course are still unknown, demonstrating the necessity to find out new key biomarkers and pathways [15,38]. In this sense, Virzì et al [39] published a review focused on the recent alternatives which may contribute to the progression of CRS, epigenetics and non-coding RNAs (ncRNAs), and extracellular vesicles (EVs), as well as new technological approaches to a better comprehension of such contribution, the omics field (proteomic, metabolomic, transcriptomic). Since these emerging molecules and technology are promising, it is crucial to revise the recent discoveries involving epigenetics, ncRNAs, and omics analysis in the AKI, cardiac hypertrophy and dysfunction, and finally CRS 3. ncR-NAs have received a simple classification considering the molecule size: small ncRNAs and long ncRNAs.…”

“…Although EVs are strictly related to kidney and heart diseases in a such way that they may be isolated from plasma and serum as predictable circulating biomarkers, much research is needed to understand the participation of these particles in CRS [39]. Exosomes have been reported to be involved in the crosstalk between heart and kidney, especially in chronic heart and renal diseases.…”

Urinary Proteomic Signature in Acute Decompensated Heart Failure: Advances into Molecular Pathophysiology

“…Kidney dysfunction in HF has generally been considered a result of impaired renal blood flow in the setting of depressed cardiac function [6]. However, increasing evidence suggests a more complex and multifactorial process [7], stressing the need to gain a better understanding of the pathophysiological mechanisms linking the failing heart and the kidney.…”