Preventing Developmental Origins of Cardiovascular Disease: Hydrogen Sulfide as a Potential Target?

The cardiovascular system can be programmed by a diversity of early-life insults, leading to cardiovascular disease (CVD) in adulthood. This notion is now termed developmental origins of health and disease (DOHaD). Emerging evidence indicates hydrogen sulfide (H2S), a crucial regulator of cardiovascular homeostasis, plays a pathogenetic role in CVD of developmental origins. Conversely, early H2S-based interventions have proved beneficial in preventing adult-onset CVD in animal studies via reversing programming processes by so-called reprogramming. The focus of this review will first summarize the current knowledge on H2S implicated in cardiovascular programming. This will be followed by supporting evidence for the links between H2S signaling and underlying mechanisms of cardiovascular programming, such as oxidative stress, nitric oxide deficiency, dysregulated nutrient-sensing signals, activation of the renin-angiotensin system, and gut microbiota dysbiosis. It will also provide an overview from animal models regarding how H2S-based reprogramming interventions, such as precursors of H2S and H2S donors, may prevent CVD of developmental origins. A better understanding of cardiovascular programming and recent advances in H2S-based interventions might provide the answers to bring down the global burden of CVD.