Table 1.

Table summarizing current studies involving MDK and cardiac pathologies. WT = wildtype; KO = knockout; IM = intramyocardial; I/R = Ischemia/Reperfusion; Tx = treatment; AdMDK = adenoviral vector overexpressing MDK; HW/BW = heart weight/body weight; MI = myocardial infarction; BNP = brain natriuretic peptide; TAC = thoracic aortic constriction; TG = transgenic.

Disease Model	Study	Animal Model	Changes in Circulating MDK	Changes in Myocardial MDK	Outcome
Ischemia/Reperfusion	Horiba et al. (2006)	♂ WT vs. MDK KO mice (12 weeks old) —IM injection of 0.008 mg/kg MDK	Not studied	WT: MDK protein peak 24 h post I/R	KO: Higher mortality, worse pathology KO + MDK: decreased infarct size
	Ishiguro et al. (2011)	♂ pigs (adult) —intracoronary injection of 0.005 mg/kg MDK	Not studied; extracellular MDK in LV in peri-infarct area	Not studied	MDK tx decreased infarct size and apoptosis
Myocardial Infarction	Fukui et al. (2007)	♂ Wistar Rats (8 weeks old) —3 doses (0.021 mg/kg; 0.12 mg/kg; 0.53 mg/kg) MDK injected in border zone	Not studied	MDK gene expression peaks 7 days post MI and MDK protein is present in border zone	MDK tx improved function, increased non-infarcted area, and increased angiogenesis in a dose-dependent manner
	Sumida et al. (2010)	♂ Wistar Rats (8–10 weeks old) —30 min after ligation inject AdMDK IM (5–6 sites; 1 × 109 PFU)	Not studied	Sham + AdMDK: high MDK protein until 8 weeks	AdMDK tx lead to improved function at 4 weeks post MI; at 6 weeks post MI: decreased collagen in non-infarct, increased angiogenesis
	Takenaka et al. (2009)	♂ WT vs. MDK KO mice (12 weeks old) —MDK administered in osmotic pumps at time of MI (4.25 mg/kg/week)	Not studied	WT: MDK expression is 7-fold higher than sham at 14 days post MI (protein MDK also increases by day 14) KO + MDK: increased MDK in peri-infarct cardiomyocytes	KO: Higher mortality KO + MDK: increased survival WT + MDK: increased survival, decreased BNP, reduced decline in function; less fibrosis, increased angiogenesis
Thoracic Aortic Constriction	Netsu et al. (2014)	♂ WT vs. MDK TG mice (8–10 weeks old)	Not studied	WT: MDK mRNA peaks 14 days post TAC; lung and kidney mRNA and protein elevated at 14–28 days	MDK TG have higher mortality decreased function, higher HW/BW, more fibrosis
Rapid pacing	Harada et al. (2014)	♂ Rabbits (2 kg) —MDK delivered by osmotic pump (1 mg/kg/week)	Not studied	Not studied	MDK tx decreased mortality; increased function, decreased apoptosis
Kidney dysfunction	Honda et al. (2016)	♂ MDK KO mice subtotal nephrectomy	Not studied	Not studied	MDK KO decreased cardiac hypertrophy