# Time-dependent integrated tissue and circulating biomarker dynamics of spexin and progranulin in an experimental myocardial infarction model

**Authors:** Sercan Kaya, Tuba Yalçin

PMC · DOI: 10.1007/s00418-026-02471-z · 2026-03-29

## TL;DR

This study examines how spexin and progranulin levels change over time in a lab model of heart attack, revealing their potential as biomarkers for heart damage.

## Contribution

The study identifies time-dependent dynamics of spexin and progranulin in an isoproterenol-induced myocardial infarction model.

## Key findings

- Spexin levels increased at 4 hours but decreased at 24 hours after ISO administration.
- Progranulin levels increased at 6 and 24 hours, suggesting a role in inflammation and cardiac remodeling.
- ISO-induced MI model showed elevated oxidative stress, inflammation, and apoptosis markers.

## Abstract

Inflammation, oxidative stress and apoptosis, in particular, play critical roles in the pathophysiology of myocardial infarction (MI). Isoproterenol (ISO) is a frequently used agent in experimental models to induce MI. This study aimed to determine the temporal changes in Spexin (SPX) and Progranulin (PRG) levels in an ISO-induced experimental MI model. The study consisted of control and ISO-treated groups (ISO-1, ISO-2, ISO-4, ISO-6 and ISO-24). In the ISO-induced MI model, serum CK-MB and troponin (I-T) levels increased, confirming cardiac damage. However, increases in oxidative parameters and decreases in antioxidant enzyme levels indicated cardiac oxidative stress. Furthermore, the time-dependent increase in inflammatory cell infiltration on histopathological examinations, paralleled by the increase in proinflammatory cytokines, confirmed the cardiac inflammatory response. Despite a decrease in cardiac antiapoptotic markers, the increase in proapoptotic marker levels reflected the temporal change in the apoptotic process induced by ISO administration. ISO administration caused SPX levels in serum and cardiac tissue to increase at 4 h and decrease at 24 h. The dynamic fluctuations in SPX levels may be related to adaptation to the stress responses and cardiac energy metabolism. ISO administration increased PRG levels in serum and cardiac tissue at 6 and 24 h. This increase suggests that PRG may contribute to a role particularly in inflammation and cardiac remodeling processes. In conclusion, the cardiac oxidative stress, inflammation and apoptosis induced by ISO administration further validated the experimental MI model. Changes in SPX and PRG levels in the ISO-induced MI model demonstrate their promise as cardiac potential markers.

## Linked entities

- **Proteins:** spx (spexin hormone), grn.L (granulin L homeolog), ckmb (creatine kinase, muscle b), LOC115584584 (troponin C, skeletal muscle)
- **Chemicals:** isoproterenol (PubChem CID 3779)
- **Diseases:** myocardial infarction (MONDO:0005068)

## Full-text entities

- **Genes:** Spx (spexin hormone) [NCBI Gene 691138] {aka Npq}, Paqr5 (progestin and adipoQ receptor family member V) [NCBI Gene 74090] {aka 0610010I15Rik, mPRg}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Tnnt3 (troponin T3, fast skeletal type) [NCBI Gene 24838] {aka Tnt}, GRN (granulin precursor) [NCBI Gene 2896] {aka CLN11, FTD2, GEP, GP88, PCDGF, PEPI}, Tnnt2 (troponin T2, cardiac type) [NCBI Gene 24837] {aka CTTG, Ctt, RATCTTG, Tnnt3}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Lgals3 (galectin 3) [NCBI Gene 83781] {aka AGE-R3, CBP30, L-34, gal-3}, Grn (granulin precursor) [NCBI Gene 29143] {aka PEPI, PGRN}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, SPX (spexin hormone) [NCBI Gene 80763] {aka C12orf39, SPX1}, Parp1 (poly (ADP-ribose) polymerase 1) [NCBI Gene 25591] {aka ARTD1, Adprt, Parp-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Lgals2 (galectin 2) [NCBI Gene 171134], Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, Tnni3 (troponin I3, cardiac type) [NCBI Gene 29248] {aka TnI, cTNI}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, PRB3 (proline rich protein BstNI subfamily 3) [NCBI Gene 5544] {aka G1, PRG}, Spx (spexin hormone) [NCBI Gene 319552] {aka B230216G23Rik, Npq}, Grn (granulin) [NCBI Gene 14824] {aka GP88, PCDGF, PEPI, Pgrn, epithelin}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887]
- **Diseases:** ischemic (MESH:D002545), atrial fibrillation (MESH:D001281), MI (MESH:D009203), metabolism disorders (MESH:D008659), cardiac edema (MESH:D004489), fatty acid metabolism disorders (MESH:D000592), Hypoxia (MESH:D000860), fibrosis (MESH:D005355), hypoxic (MESH:D002534), cardiotoxicity (MESH:D066126), myocardial necrosis (MESH:D009336), hyperoxia (MESH:D018496), cardiac remodeling (MESH:D020257), ischemic damage (MESH:D017202), edema (MESH:D004487), Inflammation (MESH:D007249), post (MESH:D000094025), injury (MESH:D014947), cardiac damage (MESH:D006331), cardiomyocyte death (MESH:D003643), infarcted myocardium (MESH:D007238), obese (MESH:D009765), cardiovascular disease (MESH:D002318), glucose and (MESH:D018149), atherosclerosis (MESH:D050197), mitochondrial damage (MESH:D028361), I/R injury (MESH:D015427), ischemia (MESH:D007511), myocardial damage (MESH:D009202)
- **Chemicals:** formalin (MESH:D005557), ROS (MESH:D017382), xylazine (MESH:D014991), paraffin (MESH:D010232), phosphate (MESH:D010710), H&amp;E (MESH:D006371), GSH (MESH:D005978), ATP (MESH:D000255), Hematoxylin (MESH:D006416), ISO (MESH:D007545), water (MESH:D014867), glucose (MESH:D005947), AEC chromogen (-), quinone (MESH:C004532), fatty acid (MESH:D005227), MDA (MESH:D008315), oxygen (MESH:D010100), catecholamines (MESH:D002395), alcohol (MESH:D000438), eosin (MESH:D004801), lipid (MESH:D008055)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

14 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13033465/full.md

---
Source: https://tomesphere.com/paper/PMC13033465